François Marchal

Nasal stimulation by water down-regulates cough in anesthetized rabbits

The cough center can be tuned by various afferent inputs, suggesting possible interactions at a central level of neural pathways originating from distant anatomical sites. The present study was designed to determine whether brief mechanical stimulation of the trachea can trigger cough during apnea elicited by nasal instillation of water. Twelve anesthetized, tracheotomized rabbits were studied. Mechanical stimulation of the trachea was performed under 3 conditions: baseline control, after instillation of saline into the nose and during apnea following instillation of water. The baseline breathing pattern did not differ between the 3 conditions. In a series of 171 stimulations, expiration reflex occurred in 81% of stimulations during apnea with a significantly (p<0.0001) lower peak expiratory flow than at baseline or during saline instillation. The incidence of responses comprising a cough reflex was also lower during water instillation than at either baseline or with saline (p<0.0001). These results indicate that stimulation of nasal afferents with distilled water likely down-regulates cough.

Down-Regulation of Cough during Exercise Is Less Frequent in Healthy Children than Adults. Role of the Development and/or Atopy?

Cough is typically associated with physical activity in children with asthma, but the characteristics of the relationship between cough and exercise has not been established under physiological conditions. The aim of the study was to describe the effect of exercise on the reflex cough response elicited by a single breath of capsaicin in non-asthmatic children. A group of non-asthmatic adults was studied as reference. Thirty children and 29 adults were recruited. The cough reflex sensitivity to capsaicin was first determined to establish the dose that provokes 5 cough efforts (C5). The number of coughs elicited by C5 (NC5) was then compared at baseline and during a standardized submaximal treadmill exercise. Data are expressed as median (interquartile range). Children and adults showed a significant decrease in NC5 (respectively from 5.0 (4.0–6.0) to 2.5 (2.0–4.0), p < 0.0005 and from 6.0 (5.0–7.0) to 2.0 (0.0–3.0, p < 0.0005). During exercise, NC5 was observed to decrease in all adult subjects, but in only 24/30 children (80%, p = 0.02). A trend for a higher incidence of personal and familial atopy was observed in children that lacked cough down-regulation during exercise compared with other children. It is concluded that the cough reflex response to capsaicin is down regulated by exercise in both children and adults. The effect however is less consistently observed in the former. The difference may reflect maturation of descending inhibitory pathways of the cough reflex, but may also be associated to atopy. The data stress the importance of assessing the time relationship of cough and exercise in questionnaire studies of asthma.

Breathing‐related changes of respiratory resistance in vocal cord dysfunction

Vocal cord dysfunction induced by exercise in children with uncontrolled asthma was identified by laryngoscopy. The paradoxical adduction of the vocal cords was also indicated by the breathing‐related changes of the forced oscillation respiratory resistance showing prominent increase during inspiration and a large positive difference between inspiration and expiration. The breathing‐related changes of respiratory resistance offer thus a useful first‐line technique to diagnose vocal cord dysfunction.

Epinephrine but not vasopressin attenuates the airway response to anaphylactic shock in rats

ABSTRACT Purpose: The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall. Aim of the Study: To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS. Materials and Methods: Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP). Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured. Results: All OVA rats died within 20 minutes following ovalbumin injection. Ovalbumin induced severe arterial hypotension and airway obstruction (221 ± 36 hPa.s.L−1 vs. vehicle 52 ± 8 hPa.s.L−1; p < 0.0001) associated with microvascular leakage distributed throughout the trachea, bronchi and intra-pulmonary airways. EPI and AVP extended survival time; EPI restored a higher level of MAP than AVP. Airway obstruction was attenuated by epinephrine (146 ± 19 hPa.s.L−1; p < 0.0001), but not by AVP (235 ± 58 hPa.s.L−1; p = 0.42). Conclusions: Epinephrine was superior to AVP for alleviating the airway response in a rat model of AS. When bronchospasm and severe arterial hypotension are present during AS, epinephrine should be the drug of choice.

Poor standardisation of plethysmographic specific airways resistance measurement despite widespread use.

Plethysmographic specific airways resistance (sRaw) has remained the most recognised measure of airway resistance for almost 60u2005years [1]. Studies in both adults and children (including preschoolers) suggest clinical utility across important obstructive lung diseases [2–5]. Measurement protocols based on rapid panting or tidal breathing exist, and are incorporated into many current commercial plethysmographs. Tidal breathing measurement offers feasibility across a wide age range, and a relatively stable index with which to distinguish effects of disease from those of growth and development [6]. Both adult and paediatric reference data exists [7, 8]; however, the wide variation in methodology existing between centres has recently been highlighted [8], and sRaw remains one of the few lung function measurements without formal standardisation guidelines [9]. Despite the wide availability of plethysmographic equipment in lung function laboratories, its use is frequently confined to lung volume measurements. Although simultaneous measures of airway resistance can easily be recorded at no extra cost, the clinical applications of sRaw remain unclear. As part of ongoing sRaw standardisation work, we sought to describe current international use of sRaw across paediatric and adult respiratory laboratories. sRaw is widely used but results should be interpreted with caution until its recording is better standardised http://ow.ly/QvJRJ

Biphasic airway–lung response to anaphylactic shock in Brown Norway rats

Bronchospasm may be part of the response to systemic anaphylaxis in humans. The anaphylactic shock has been characterized in allergic rats, but little data are available on the concurrent changes in airway-lung mechanics. The aim was to describe the respiratory resistance (Rrs) and reactance (Xrs) response to ovalbumin (OVA) induced systemic anaphylaxis in allergic rats. Thirty five anesthetized and mechanically ventilated Brown Norway rats were randomly allocated to OVA (n=20) or vehicle (n=15) sensitization and provocation. Rrs and Xrs were obtained by the forced oscillation technique at 20 Hz. Allergic rats showed dramatic and reproducible concurrent Rrs peak and Xrs through within 4 min of OVA injection (p<0.0001). Thereafter, Rrs returned to baseline while Xrs remained significantly more negative (p<0.0001). It is concluded that systemic anaphylaxis in allergic rats is associated with severe early acute inhomogeneous bronchoconstriction followed by pulmonary interstitial/small airspace edema. The model may be of interest to assess treatments targeting the associated bronchoconstriction and/or airway vascular leakage.

Modulation of defensive airway reflexes during continuous positive airway pressure in the rabbit

Lung hyperinflation may alter the pattern of ventilatory reflexes in chronic respiratory disorders. The aim of the study was to test the effect of continuous positive airway pressure (CPAP) on ventilatory responses to mechanical stimulation of the trachea.

Specific airway resistance in preschool children: why not panting after all?

Specific airway resistance (sRaw) is measured with minimal cooperation in the preschool child during tidal breathing [1]. Methodological difficulties have been encountered in modern plethysmographs when the warming and humidification of the inspired gas [2] are replaced by numerical algorithms to eliminate the thermo hygrometric artefact [1, 3, 4]. Measuring sRaw during panting [5] had been dismissed in preschool children based on the assumption that the ventilatory manoeuvre would be difficult to perform and standardise. The feasibility of such an assumption, however, has not been verified. Therefore, the aim of this study was to assess the feasibility of measuring sRaw during panting in preschool children with asthma and compare the outcome with the tidal breathing method. Specific airway resistance may be measured in preschool children during routine lung function http://ow.ly/pvxr3034Bo8

More Relaxation by Deep Breath on Methacholine- Than on Exercise-Induced bronchoconstriction during the Routine Testing of Asthmatic Children

Deep inspiration (DI) dilates normal airway precontracted with methacholine. The fact that this effect is diminished or absent in asthma could be explained by the presence of bronchial inflammation. The hypothesis was tested that DI induces more relaxation in methacholine induced bronchoconstriction—solely determined by the smooth muscle contraction—than in exercise induced bronchoconstriction, which is contributed to by both smooth muscle contraction and airway wall inflammation. The respiratory conductance (Grs) response to DI was monitored in asthmatic children presenting a moderately positive airway response to challenge by methacholine (n = 36) or exercise (n = 37), and expressed as the post- to pre-DI Grs ratio (GrsDI). Both groups showed similar change in FEV1 after challenge and performed a DI of similar amplitude. GrsDI however was significantly larger in methacholine than in exercise induced bronchoconstriction (p < 0.02). The bronchodilatory effect of DI is thus less during exercise- than methacholine-induced bronchoconstriction. The observation is consistent with airway wall inflammation—that characterizes exercise induced bronchoconstriction—rendering the airways less responsive to DI. More generally, it is surmised that less relief of bronchoconstriction by DI is to be expected during indirect than direct airway challenge. The current suggestion that airway smooth muscle constriction and airway wall inflammation may result in opposing effects on the bronchomotor action of DI opens important perspective to the routine testing of asthmatic children. New crossover research protocols comparing the mechanical consequences of the DI maneuver are warranted during direct and indirect bronchial challenges.

Bronchial or Laryngeal Obstruction Induced by Exercise

A child suspected of exercise-induced laryngeal obstruction and asthma is examined by laryngoscopy and respiratory resistance (Rrs) after exercise challenge. Immediately at exercise cessation, the visualized adduction of the larynx in inspiration is reflected in a paroxystic increase in Rrs. While normal breathing has apparently resumed later on during recovery from exercise, the pattern of Rrs in inspiration is observed to reoccur following a deep breath or swallowing. The procedure may thus help diagnosing the site of exercise-induced obstruction when laryngoscopy is not available and identify re-inducers of laryngeal dysfunction.