Both exhaled nitric oxide and blood eosinophil count were associated with mild allergic asthma only in non-smokers.

BACKGROUND: The fractional exhaled nitric oxide (FENO) and the blood eosinophil count (B-eos) are markers of eosinophilic inflammation used in the diagnosis and management of asthma. The relationships between smoking cigarette and both FENO and B-eos are complex and raise questions about the association between these markers and asthma in smokers. OBJECTIVE: To determine the relationships between both FENO and B-eos on one hand and asthma and atopy on the other, according to smoking status. METHODS: FENO and B-eos were measured in, respectively, 1579 and 1496 of the 1607 middle-aged adults randomly selected from the general population in the cross-sectional ELISABET survey. Allergic asthma was defined as asthma (a self-report of physician-diagnosed asthma, and wheezing in the previous 12 months or the use of asthma medications) with atopy (allergic rhinitis or hayfever in the previous 12 months, or a previous positive prick test or allergen desensitization therapy). Non-allergic asthma was defined as asthma without atopy. RESULTS: The analysis included 812 (51.4%) never, 473 (30%) former and 294 (18.6%) current smokers. A total of 490 (32%) participants were atopic, 80 (5.1%) had allergic asthma, and 31 (2%) had non-allergic asthma. Only 16.2% (18/111) of asthmatics were treated with glucocorticoid inhalants, suggesting that among them a majority of participants had mild asthma. A positive interaction between smoking status and allergic asthma was observed in multivariate models explaining FENO (P = 0.003) and B-eos (P = 0.001). Thus, compared to those without allergic asthma, participants with allergic asthma had higher FENO values (+ 63.4%, 95% CI = [39; 92]) and higher B-eos (+ 63.2% [38.2; 92.7]) in never and former smokers, but not in current smokers. Lastly, an analysis of receiver-operating characteristic curves showed that each of the two markers was able to discriminate moderately allergic asthma but only in non-smokers. CONCLUSIONS & CLINICAL RELEVANCE: FENO and B-eos were associated with the presence of mild allergic asthma only in non-smokers, not in current smokers. These findings raise questions about the clinical value of FENO and B-eos in smokers.

A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.

BACKGROUND: Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. OBJECTIVE: We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. METHODS: We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N = 610 adults) and the Hutterites (N = 601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N = 450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N = 8858) consortium. RESULTS: We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P = 1.6 × 10(-7) ) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P = 8.9 × 10(-7) ) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. CONCLUSIONS AND CLINICAL RELEVANCE: This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.

Home telemonitoring (forced expiratory volume in 1 s) in children with severe asthma does not reduce exacerbations.

Some children with severe asthma develop frequent exacerbations despite intensive treatment. We sought to assess the outcome (severe exacerbations and healthcare use, lung function, quality of life and maintenance treatment) of a strategy based on daily home spirometry with teletransmission to an expert medical centre and whether it differs from that of a conventional strategy. 50 children with severe uncontrolled asthma were enrolled in a 12-month prospective study and were randomised into two groups: 1) treatment managed with daily home spirometry and medical feedback (HM) and 2) conventional treatment (CT). The children's mean age was 10.9 yrs (95% confidence interval 10.2-11.6). 44 children completed the study (21 in the HM group and 23 in the CT group). The median number of severe exacerbations per patient was 2.0 (interquartile range 1.0-4.0) in the HM group and 3.0 (1.0-4.0) in the CT group (p=0.38 with adjustment for age). There were no significant differences between the two groups for unscheduled visits (HM 5.0 (3.0-7.0), CT 3.0 (2.0-7.0); p=0.30), lung function (pre-ß(2)-agonist forced expiratory volume in 1 s (FEV(1)) p=0.13), Paediatric Asthma Quality of Life Questionnaire scores (p=0.61) and median daily dose of inhaled corticosteroids (p=0.86). A treatment strategy based on daily FEV(1) monitoring with medical feedback did not reduce severe asthma exacerbations.

Self-regulation of exercise intensity by estimated time limit scale.

The purpose of this study was to evaluate the validity of the estimated time limit scale (ETL), which deals with a subjective prediction of how long the current exercise intensity can be maintained, for regulating exercise intensity using typical estimation-production procedure. Thirty-six male athletes performed a continuous incremental test and two discontinuous tests with randomized workloads (estimation tests at 65, 75, 85 and 95% of the maximal power output, and production tests: subjects have to use the ETL values which were collected for each power during the estimation test in order to manually product the corresponding workload). The intraclass correlation coefficient for the power output between estimation and production tests is good for exercises at 75, 85 and 95% MAP (0.81, 0.85 and 0.96, respectively). Moreover, mean differences both for power output and cardiorespiratory data were not significantly different between estimation and production tests for exercises at 85 and 95% MAP. Consequently, the validity to prescribe an exercise intensity from the ETL scale is attested in these athletes particularly for high exercise intensities on cycloergometer.

Dramatic impact of morbid obesity on child lung development.

OBJECTIVE: To assess the respiratory function and sleep characteristics of obese adults and children. METHODS: All patients with non-syndromic, severe obesity (BMI ≥3 z-scores for children and ≥40.00kg/m2 for adults), referred for pulmonary function tests at Lille University Hospital, were retrospectively included. RESULTS: A total of 69 children (mean±SD BMI 36.8±6.7 and mean BMI z-score 4.7±1.0) and 70 adults were included (mean BMI 45.7±6.2). Metabolic syndrome was diagnosed in 13 children (26%) and 40 adults (80%). Reduced lung volumes were observed in 34 children (50.0%) and 16 adults (24.0%) and both the mean functional residual capacity (FRC) and the mean residual volume (RV) were lower in children than in adults (FRC: -1.7±2.1 z-score in children vs. -1.0±1.1 in adults, P=0.026; and RV: -0.8±1.2 z-score in children vs. -0.1±1.1 in adults, P=0.002). The prevalence of severe obstructive sleep apnea syndrome was greater in adults (40.7% vs. 18.8%, P=0.007). Children had a higher average oxygen saturation (median of 96.0% [91.0-98.0] vs. 93.0% [76.0-97.0] in adults, P<0.0001). CONCLUSION: Obesity has consequences for lung volumes in children; however, a longitudinal study is needed to determine the impact on pulmonary expansion and growth.

The Borg dyspnoea score: a relevant clinical marker of inspiratory muscle weakness in amyotrophic lateral sclerosis.

The aim of the study was to determine whether the Borg dyspnoea scale could be a useful and simple marker to predict respiratory muscle weakness in amyotrophic lateral sclerosis (ALS). From April 1997 to 2001, respiratory function was perfomed in 72 patients together with the Borg score in both the upright (uBorg) and supine (sBorg) positions. Mean upright vital capacity (VC) was 81+/-24% predicted, sniff nasal inspiratory pressure (SNIP) was 55+/-26% pred, maximal inspiratory pressure (P(I,max)) was 57+/-26% pred and arterial carbon dioxide tension (P(a,CO(2))) was 41+/-6 mmHg. The mean Borg scores in the upright and supine positions were 1.7+/-1.5 and 2.2+/-2, respectively. A significant relationship between SNIP and uBorg (r = 0.4; p = 0.0007) and SNIP and sBorg (r = 0.58; p<0.0001) was observed. Upright VC, DeltaVC (measured as the supine fall in VC as a percentage of seated VC), P(I,max) and P(a,CO(2)) were significantly correlated with SNIP. A cut-off value of 3 on the sBorg scale provided the best sensitivity (80%) and specificity (78%) (area under the curve 0.8) to predict a SNIP < or =40 cmH(2)O, indicating severe inspiratory muscle weakness. Patients with a sBorg score > or =3 also exhibited significantly lower VC, P(I,max) and twitch mouth pressure during cervical magnetic stimulation, and slightly higher P(a,CO(2)) (43.7+/-7 versus 39.2+/-5 mmHg; p = 0.05). The Borg dyspnoea scale is a valuable noninvasive test for the prediction of inspiratory muscle weakness in ALS patients.

Cryptogenic haemoptysis in smokers: angiography and results of embolisation in 35 patients.

The aim of the present study was to describe angiographic findings and embolisation results in smokers with haemoptysis. We retrospectively reviewed the clinical data and angiographic findings from 35 patients with smoking-related bronchopulmonary disease and no associated comorbidity, who were referred for embolisation for mild (n = 6), moderate (n = 14) and severe (n = 15) haemoptysis. Spirometric classification subdivided our population into: 16 patients with chronic bronchitis but no airflow limitation; and 19 patients with chronic obstructive pulmonary disease (COPD) (stage I: n = 12; stage II: n = 5; stage III: n = 2). Bronchoscopy depicted focal submucosal vascular abnormalities in three patients and only endobronchial inflammation in 32 (91%) patients. Bronchial artery angiography revealed moderate (n = 18) or severe (n = 10) hypervascularisation in 28 (80%) patients, and normal vascularisation in seven (20%). No statistically significant difference was observed between the angiographic findings and the severity of COPD, tobacco consumption or the amount of bleeding. Cessation of bleeding was obtained by embolisation in 29 out of the 34 technically successful procedures (85%), requiring surgery in three out of five patients with recurrence. Follow-up (mean duration 7 yrs) demonstrated no recurrence of bleeding in 32 (94%) out of 34 patients and excluded late endobronchial malignancy. Smokers with various stages of COPD severity may suffer from haemoptysis that is efficiently treatable by endovascular treatment.

Why does exercise terminate at the maximal lactate steady state intensity?

OBJECTIVE: The purpose of this study was to measure physiological responses during exercise performed until exhaustion at the exercise intensity corresponding to the maximal lactate steady state (MLSS) in order to determine why subjects stopped. METHODS: Eleven male trained subjects performed a test at MLSS on a cycle ergometer until exhaustion. RESULTS: Time to exhaustion was 55.0 (SD 8.5) min. No variation was observed between the 10th and the last minute for arterial pyruvate, bicarbonate, and haemoglobin concentrations, redox state, arterial oxygen pressure, arterial oxygen saturation, osmolality, haematocrit, oxygen uptake, carbon dioxide output, and gas exchange ratio (p>0.05). Arterial lactate concentration and arterial carbon dioxide pressure decreased significantly whereas pH, base excess and the Ratings of Perceived Exertion (RPE) increased significantly (p<0.05). Although respiratory rate, minute ventilation and heart rate increased significantly until exhaustion (p<0.05), values at termination of the MLSS test were significantly lower than values measured during a maximal exercise test (p<0.05). Blood ammonia concentrations rose progressively during the MLSS test. However, there is no known mechanism by which this change could cause peripheral fatigue. CONCLUSIONS: Exercise termination was not associated with evidence of failure in any physiological system during prolonged exercise performed at MLSS. Thus the biological mechanisms of exercise termination at MLSS were compatible with an integrative homoeostatic control of peripheral physiological systems during exercise.

[Effect of thoracic bracing on lung function in children with neuromuscular disease]. / Impact du corset thoracique sur la fonction respiratoire chez des enfants atteints de maladie neuromusculaire.

UNLABELLED: Respiratory muscle weakness associated with scoliosis in neuromuscular disease leads to respiratory impairment. Children with scoliosis are usually treated with spinal bracing to delay the progress of disease. We studied the impact of spinal bracing on lung function in these children. METHODS: Retrospective study of patient data from January 1997 to January 2003. Spirometry and measurement of lung volume involved 32 observations, corresponding to 17 children with neuromuscular disease, including 14 with spinal muscular atrophy. Data for children with and without a brace were studied. RESULTS: A total of 72% of the children had severe scoliosis (Cobb score>30 degrees ); 40% wore a Garchois brace. Children without a brace showed a mean vital capacity of 65% of predicted value, with a restrictive syndrome in 44% of observations. Children with a brace showed significantly reduced vital capacity (-4.6%; P<0.001) and forced expiratory volume in 1 s (-4.6%; P=0.002). The reduced vital capacity was lower in children with the Garchois brace: -1% (P=0.02). Severity of scoliosis and measured volumes were not related. CONCLUSION: Spinal bracing in children with neuromusclar disease leads to significant respiratory impairment. Assessment of pulmonary function is necessary when a brace is indicated. The Garchois brace might lead to less impairment of respiratory function.

[Walking tests: a step forward for functional cardiorespiratory assessment]. / Tests de marche: une avancée dans l'évaluation fonctionnelle cardiorespiratoire.

Exercise testing provides information on physical capacity during exercise in addition to spirometric measures of lung function or assessment on treadmills or ergonomic cycle. The "gold standard" assessment of exercise tolerance is measured in the laboratory using treadmills or ergonomic cycle but the necessary equipment is expensive and may not be readily accessible; such tests require people used to work with children. Walking tests are field tests providing a valid and easily accessible method of measuring function-limited exercise tolerance in patients with respiratory or cardiac chronic diseases. These walking tests are non-threatening, inexpensive, easy to perform and to understand for children. Walking tests performed in daily practice are the following: "time-based" tests (2-, 6- or 12-min walking test), 3-min step test (on a step) and the shuttle walking test. It may be a useful measure to assess therapeutic intervention and provide information on the prognosis. They are simple and safe methods to evaluate quality of life in these patients.

[Methacholine challenge in young children: measurement of resistance by interruption]. / Test a la métacholine chez le jeune enfant: Mesure de la résistance par interruption.

The aims of this study were 1. To evaluate the measurement of resistance by interruption (Rint) of bronchoconstriction induced by inhalation of methacholine and 2. To determine a threshold of increase of resistance in young children to differentiate responders from non-responders. Forty-six children (mean age 5 [4.3-6.1] years) referred for methacholine challenge were tested by measurement of Rint and transcutaneous oxygen tension. A fall of 20% or more in oxygen tension from the baseline was used to define the responders. The children studied had a baseline Rint significantly higher than normal (0.84 [0.68-1.01] vs. 0.76 [0.60-0.90] kPa L(-1)s; p < 0.03). Forty-one children were responders and had an increase in Rint significantly different from the non-responders (p < 0/04). An increase in Rint of 35% distinguished responders from non-responders in young children with chronic cough. Interrupter resistance increases significantly during bronchial provocation in responding young children and may be used to measure the degree of bronchoconstriction.

[Genetic and environmental factors of asthma and allergy: Results of the EGEA study]. / Facteurs génétiques et environnementaux de l'asthme et de l'allergie: synthèse des résultats de l'étude EGEA.

INTRODUCTION AND METHODS: The EGEA study (epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), which combines a case-control and a family-based study of asthma case (n=2120 subjects) with three surveys over 20 years, aims to identify environmental and genetic factors associated with asthma and asthma-related phenotypes. We summarize the results of the phenotypic characterization and the investigation of environmental and genetic factors of asthma and asthma-related phenotypes obtained since 2007 in the EGEA study (42 articles). RESULTS: Both epidemiological and genetic results confirm the heterogeneity of asthma. These results strengthen the role of the age of disease onset, the allergic status and the level of disease activity in the identification of the different phenotypes of asthma. The deleterious role of active smoking, exposure to air pollution, occupational asthmogenic agents and cleaning products on the prevalence and/or activity of asthma has been confirmed. Accounting for gene-environment interactions allowed the identification of new genetic factors underlying asthma and asthma-related traits and better understanding of their mode of action. CONCLUSION: The EGEA study is contributing to the advances in respiratory research at the international level. The new phenotypic, environmental and biological data available in EGEA study will help characterizing the long-term evolution of asthma and the factors associated to this evolution.

Electrophysiological effects of corticosteroids on the retinal pigment epithelium.

PURPOSE: As corticosteroids appear to intervene in pathogenesis of central serous chorioretinopathy, ion transport changes within the retinal pigment epithelium (RPE) might be involved. Electrophysiological responses to corticosteroid administration were recorded in vivo and in vitro. METHODS: Clinical study: The standing ocular potential was recorded during intravenous (IV) infusion of glucose 5% and glucose 5% + prednisolone 0.2% in 14 patients with relapsing multiple sclerosis. The results were compared with a control group receiving two successive identical glucose 5% infusions. In vitro study: Native tissue explants (RPE + choroid, porcine, and bovine) were placed in a Ussing-type chamber. After baseline determination of the transepithelial potential (PD), short circuit current (I(sc)) and transepithelial resistance (R(t)), the effect of apical hydrocortisone (HC) 10(-4) M was determined. RESULTS: Clinical study: A significant rise of the standing potential was found after glucose infusion (P = 0.005), whereas no change was detected after IV glucose + prednisolone (P = 0.695). In vitro study: In the porcine RPE, the mean baseline PD and I(sc) were significantly reduced (both P: = 0.012) after applying apical 10(-4) HC. R(t) was also significantly reduced (P = 0.01). The same type of response, observed in bovine RPE, was reduced in low chloride/low bicarbonate conditions. CONCLUSIONS: Corticosteroids modified electrophysiological parameters representing RPE function in vivo. The existence of an RPE-specific effect was confirmed in vitro. Further work is required to link the observed ion transport changes to a reduction of apical, subretinal fluid absorption.

Influence of epithelium on the responsiveness of guinea-pig isolated trachea to adenosine.

1. The influence of epithelium removal on the effects of adenosine on airway contractility was investigated on the guinea-pig isolated trachea. 2. In preparations under resting tone or precontracted with histamine 10(-5) M, removal of the tracheal epithelium resulted in similar shifts to the left of the adenosine concentration-response curves (0.61 +/- 0.18 (P less than 0.05) and 0.80 +/- 0.09 (P less than 0.001) log units; n = 5), corresponding to 4.07 and 6.31 fold potentiations of the relaxant effect of adenosine. 3. In the presence of dipyridamole 10(-5) M the relaxant effects of adenosine were potentiated 85.1 fold on tracheae with epithelium; removal of the epithelium did not produce a significant additional shift to the left of the adenosine concentration-response curves (0.07 +/- 0.03 log units; n = 5; NS). 4. In the absence of dipyridamole, the theophylline-adenosine antagonism was not of the competitive type, irrespective of whether the tracheae were with or without epithelium. 5. In the presence of dipyridamole, this antagonism was likely to be of the competitive type and its characteristics were the same when the epithelium was present or absent. Regression slope and pA2 values were 0.84 and 5.07, respectively, in the presence of epithelium and 0.76 and 4.89, respectively, in its absence. 6. It is suggested that, at least in the guinea-pig isolated trachea model, the airway epithelium seems to be involved only in the uptake and metabolism of adenosine.

Effect of nedocromil sodium on allergen-, PAF-, histamine- and bradykinin-induced airways vasodilatation and pulmonary obstruction in the pig.

1. The influence of nedocromil sodium on the nasal and bronchial effects induced by allergen, platelet-activating factor (PAF), capsaicin, histamine and bradykinin aerosol challenge in ascaris-sensitized and pentobarbitone-anaesthetized pigs was studied. Blood flow changes in the bronchial and nasal circulation were measured with ultrasonic flow probes around the supplying arteries, and vascular resistance was calculated. Changes in pulmonary resistance (Rpulm), dynamic compliance (Cdyn), mean arterial pressure (MAP) and heart rate (HR) were also determined. 2. Allergen and PAF aerosol challenge in the lung produced similar effects consisting of both bronchial and nasal vasodilatation, bronchoconstriction (increase in Rpulm and decrease in Cdyn) and increases in MAP and HR. Local pretreatment with nedocromil sodium (80 mg, aerosol) reduced the peak and duration of both the bronchial vasodilatation and increase in Rpulm, while only the duration of the change in Cdyn was significantly decreased. Nedocromil sodium did not alter the increases in MAP and HR. The nasal vasodilatation evoked by PAF, but not allergen, challenge in the lung was reduced by nedocromil sodium. 3. Allergen challenge in the nose induced vasodilatation of long duration which was reduced by local nedocromil sodium pretreatment (50 micrograms kg-1, intra-arterially). 4. The vasodilator response to histamine aerosol was attenuated in the nasal, but not the bronchial circulation by local nedocromil sodium pretreatment. Histamine-induced bronchoconstriction was not altered by nedocromil sodium. 5. Bradykinin aerosol-induced vasodilatation in the nasal and bronchial circulation was markedly and equally reduced by local nedocromil sodium and systemic capsaicin (50 mg kg-1, s.c. 2 days before) pretreatment. 6. In conclusion, nedocromil sodium blocks some local vascular and bronchial effects, but not increases in MAP and HR, induced by allergen and PAF aerosol in the pig. Bradykinin-induced vasodilatation in the airways, which seems to be largely dependent on capsaicin-sensitive sensory nerves, is markedly inhibited by nedocromil sodium pretreatment, whereas capsaicin-induced vasodilatation is not affected by nedocromil sodium. It may be suggested that nedocromil sodium acts by inhibiting some common process involved in the release of mediators from inflammatory cells (when stimulated by allergen and PAF) and sensory nerves (when stimulated by bradykinin and histamine, but not capsaicin).

Cigarette smoke, nicotine and capsaicin aerosol-induced vasodilatation in pig respiratory mucosa.

1. Anesthetized pigs were used to study vascular responses in the sphenopalatine artery (SPA), superior laryngeal artery (SLA) and bronchial artery (BA) upon exposure to cigarette smoke or aerosol of nicotine and capsaicin. Direct blood flow recordings were made with ultrasonic probes around the vessels. 2. Smoke from one cigarette was administered as inhalation for 2 min with or without a Cambridge filter which removes the particulate matter including nicotine from the smoke. Aerosols of nicotine (2.5 mg) or capsaicin (10 mg) were administered to the nose or the lower airways for 3 min. 3. Cigarette smoke exposure caused a reproducible reduction of the vascular resistance (VR) suggesting vasodilatation in the SPA, SLA, and especially the BA. The vasodilatation was not modified by the Cambridge filter, suggesting that it was caused by vapour phase components rather than nicotine. 4. The smoke effect was not changed after pretreatment with the cyclo-oxygenase inhibitor, diclofenac, or with atropine, guanethidine, H1- or H2-histamine receptor antagonists, nedocromil, or by vagotomy. The smoke-evoked decrease in VR was not modified by the nicotinic receptor antagonist chlorisondamine in the SLA or BA. 5. In pigs pretreated with increasing doses of capsaicin two days earlier, the decrease in VR upon smoke exposure in both the BA and SLA was unaffected while the change in VR was attenuated in the SPA. 6. Nicotine aerosol had no effect on VR in the peripheral airways supplied by the BA while a decrease in VR was observed in the SLA and SPA. The nicotine response was reduced after capsaicin pretreatment in the nasal and upper tracheal circulation. 7. Capsaicin aerosol reduced VR in the vascular beds supplied by the SPA, SLA and BA and this response was markedly reduced after capsaicin pretreatment. 8. The mechanisms underlying vasodilatation upon cigarette smoke exposure in the bronchial mucosa are at the moment unclear while both non-cholinergic parasympathetic and sensory components may be involved in the nose. Capsaicin induced a vasodilatation at all levels via sensory mechanisms, whereas nicotine-evoked vasodilatation is restricted to the upper airway mucosa and is at least partly dependent on parasympathetic reflexes involving capsaicin-sensitive sensory nerves.

Effects of nasal continuous positive airway pressure (NCPAP) on breathing pattern in spontaneously breathing premature newborn infants.

OBJECTIVE: The aim of the study was to assess the influence of nasal continuous positive airway pressure (NCPAP) on breathing pattern in preterm newborns. DESIGN: Prospective study. SETTING: Neonatal intensive care unit. PATIENTS: Ten premature newborn infants on NCPAP (gestational age range from 27 to 32 weeks, mean birth weight 1300+/-460 g) admitted in our neonatal intensive care unit (NICU) for respiratory distress syndrome. METHODS: Breathing patterns and changes in lung volumes level were obtained using respiratory inductive plethysmography (RIP), at random CPAP levels (0, 2, 4, 6 and 8 cmH2O). Raw data were analysed for end-expiratory lung volume level (EELV-level), tidal volume (Vt), respiratory rate, phase angle and labour breathing index (LBI). RESULTS: CPAP increased EELV-level by 2.1+/-0.3xVt from 0 to 8 cmH2O ( p<0.01). Vt increased by 43% from CPAP of 0 cmH2O to CPAP of 8 cmH2O ( p<0.01). We also found that CPAP lowered the phase angle (from 76+/-21 degrees at CPAP of 0 cmH2O to 30+/-15 degrees at CPAP of 8 cmH2O; p<0.01 ) and LBI (from 1.7+/-0.8 at CPAP of 0 cmH2O to 1.2+/-0.3 at CPAP of 8 cmH2O; p<0.05). CONCLUSION: NCPAP improves the breathing strategy of premature infants with respiratory failure, as reflected by improved thoraco-abdominal synchrony, increased Vt and reduction of the LBI. This effect is associated with an increase in EELV-level with CPAP level. However, further investigations are necessary to establish the best CPAP level that ensures both safety and efficiency.

Inhibition of cholinergic and non-adrenergic, non-cholinergic bronchoconstriction in the guinea pig mediated by neuropeptide Y and alpha 2-adrenoceptors and opiate receptors.

The mechanisms underlying the regulatory influence of neuropeptide Y (NPY) and of alpha 2-adrenoceptor and opiate receptor activation on cholinergic and excitatory non-adrenergic, non-cholinergic (e-NANC) neurotransmission were studied in guinea pig hilus bronchi in vitro. NPY inhibited both the cholinergic and e-NANC bronchial contractions evoked by field stimulation. The NPY attenuation of the e-NANC contraction could not be antagonized by the alpha 2-antagonist, idazoxan, or naloxone. UK 14,304 a specific alpha 2-agonist, also reduced the two nervous components of bronchial contraction and this action was inhibited by idazoxan. NPY and UK 14,304 exerted a minor influence on the bronchial smooth muscle tone per se or on contractions evoked by acetylcholine or neurokinin A. This suggested that the inhibitory responses were caused by a prejunctional action reducing the release of transmitter substances from sensory and cholinergic nerve endings. Furthermore NPY (10(-7) M) seemed to be more potent to inhibit both contractile components than noradrenaline (10(-6) M) in the presence of propranolol (3 X 10(-6) M). Morphine was able to reduce the e-NANC response via a naloxone-sensitive mechanism. The capsaicin-evoked bronchoconstriction and the bronchodilator NANC effect evoked by field stimulation were, however, not influenced by UK 14,304. It is concluded that NPY, alpha 2-receptor and opiate receptor activation inhibit the release of sensory transmitters evoked by field stimulation but not by capsaicin.

Occurrence, specific binding sites and functional effects of endothelin in human cardiopulmonary tissue.

Endothelin (ET)-like immunoreactivity (-LI) was detected in the human cardiopulmonary system, with the highest levels being found in the left anterior descending coronary artery, followed by the lung, right atrium, pulmonary artery, bronchus, pulmonary vein and left ventricle. Chromatographic characterization showed that the ET-LI in the lung and left ventricle corresponded to synthetic ET-1. Specific, high-affinity binding sites for ET-1, with an extremely slow dissociation rate, were found in the lung, right atrium and left ventricle. Displacement studies revealed a rank order of potency of ET-1 greater than ET-2 and sarafotoxin 6b greater than ET-3 and big ET-1. Scatchard analysis indicated a single receptor population in the lung (KD 1.53 x 10(-10) M) and left ventricle (KD 3.0 x 10(-11) M). In functional experiments, ET-1 evoked concentration-dependent, long-lasting vasoconstriction of a higher potency than that evoked by ET-2 and ET-3 in epicardial coronary arteries as well as in pulmonary arteries. ET-1 and ET-2 also showed bronchoconstrictor activity at considerably lower concentrations (threshold 10(-11) M) of ET-1 than those needed to cause vasoconstriction (10(-9) M). ET-LI, mainly consisting of ET-1, occurs in human cardiopulmonary tissue. Specific, high-affinity sites with irreversible binding for ET-1 are found in both the heart and lung. ET-1 is more potent than ET-2 or ET-3 in displacing ET-1 binding and in causing vasoconstriction and bronchoconstriction. Thus, in the human heart and lung, ET-1 seems to be the most abundant and biologically active of the endothelin peptides.

Vagal vasodilatory mechanisms in the pig bronchial circulation preferentially involves sensory nerves.

The present study shows that in contrast to the upper trachea, where the parasympathetic vasodilatory components of both cholinergic and non-cholinergic nature are dominating, the vagal blood flow regulation in the peripheral airways of the pig supplied by the bronchial artery is entirely carried out by local release of vasodilatory mediators from capsaicin-sensitive sensory nerves. Also inhalation of the vapour phase from the major airway irritant cigarette smoke was associated with a marked increase in bronchial blood flow possibly via local axon reflexes. Capsaicin, substance P (SP) and calcitonin gene-related peptide (CGRP) caused vasodilatation in both the trachea and bronchi while vasoactive intestinal polypeptide (VIP) was most active in the trachea. These functional data were supported by immunohistochemical studies showing the presence of SP- and CGRP-containing nerves of presumably sensory origin around bronchial blood vessels while VIP-positive perivascular fibres of local parasympathetic origin were found mainly in the trachea.