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.

Desensitization of the cough reflex during limb muscle contraction in anesthetized rabbits.

The 'cough network' exhibits plasticity at the sensor and integration levels leading to modulation of the strength or pattern of the cough reflex. Little is known about the interactions between cough and human activities, especially during exercise. The present study was designed to determine whether exercise, mimicked by electrically induced muscle contractions, can modify the incidence and/or strength of cough following mechanical stimulation of the trachea in anesthetized rabbits. Thirteen anesthetized, tracheotomized rabbits were studied by a total of 311 tracheal stimulations: 196 at rest and 115 during exercise. During muscle contractions, the incidence of the cough reflex (CR) decreased and the expiration reflex (ER) increased (p < 0.0001). The sensitivity of the CR and ER both decreased during exercise compared to the sensitivity of the CR at rest (p < 0.02), while the strength of the expulsive response remained unchanged. These results indicate that adjustments occurring during muscle contractions likely downregulate tracheal defensive reflexes in anesthetized rabbits.

Exercise-induced bronchoconstriction in school-age children born extremely preterm.

BACKGROUND: School children born preterm often show airway hyperresponsiveness to methacholine or histamine. Less attention has been paid to their airway response to exercise, an important point because of the role of exercise in the child's daily life. The aim of this study was to describe the characteristics of, and potential determinants to, the airway response to exercise in children born extremely preterm. METHODS: Forty-two nonasthmatic nonatopic children born before 32 wk gestation were compared with 27 healthy nonasthmatic nonatopic term children at age 7. Spirometry and respiratory impedance were measured at baseline and repeated after a single-step 6-min treadmill exercise in a climate-controlled room. RESULTS: The preterm group showed significant broncho-constriction induced by exercise. Prematurity, but not low baseline lung function, neonatal oxygen supplementation, mechanical ventilation, chronic lung disease, or maternal smoking, was a determinant of exercise-induced bronchoconstriction. CONCLUSION: Children born extremely preterm present significant exercise-induced airway obstruction at age 7. The response has different characteristics from that occurring in asthmatics and is likely to express airway noneosinophilic inflammation.

Airway response to exercise by forced oscillations in asthmatic children.

Forced expiratory volume in 1 s (FEV1) detection of exercise-induced bronchoconstriction (EIB) to identify asthma has good specificity but rather low sensitivity. The aim was to test whether sensitivity may be improved by measuring respiratory resistance (Rrs) by the forced oscillation technique (FOT). Forty-seven asthmatic and 50 control children (5-12 y) were studied before and after running 6 min on a treadmill. Rrs in inspiration (Rrsi) and expiration (Rrse), FEV1 and Rrsi response to a deep inhalation (DI) were measured before and after exercise. In asthmatics versus controls, exercise induced significantly larger increases in Rrsi (p < 0.001) and larger decreases in FEV1 (p = 0.004). Asthmatics but not controls showed more bronchodilation by DI after exercise (p = 0.02). At specificity >0.90, sensitivity was 0.53 with 25% increase Rrsi and 0.45 with 27% increase Rrse or 5% decrease FEV1. It is concluded that the FOT improves sensitivity of exercise challenge, and the Rrsi response to DI may prove useful in identifying the mechanism of airway obstruction.

Within breath ventilatory responses to mechanical tracheal stimulation in anaesthetised rabbits.

Ventilatory responses to airway mechanical stimulation usually consist in mixed cough (CR) and expiration (ER) reflexes. The stimulus characteristics that would favour either reflex may vary with breathing, but the issue cannot be addressed with the usual long lasting stimulus. The aim of the study was to describe respiratory responses evoked by a punctuate tracheal stimulus and their relationship to inspiration and expiration. Experiments were repeated after bronchoconstriction. Eight anesthetized tracheotomized rabbits were stimulated in the trachea by 150 ms probing before and after methacholine inhalation (248 tests). CR and ER were evaluated from tidal volume and expiratory flow. The overall incidence of responses was larger in inspiration than expiration (p < 0.0001). A majority of responses were single CR or ER, also strongly related to breathing: 93% CR occurred with the stimulus in inspiration and 78% ER with the stimulus in expiration (p = 0.001). Bronchoconstriction did not change the incidence of single efforts, increased that of mixed responses and decreased the amplitude of preparatory and expulsive phases of CR. The study demonstrates the strong dependence of CR and ER on the phase of breathing and adds to the current evidence that regulating mechanisms clearly differ for each reflex.

A systematic review of lung function testing in asthmatic young children.

Asthma diagnosis is difficult in young children being mainly based on clinical signs and parents' history, which is sometimes difficult to obtain. Lung function testing may improve asthma diagnosis by objectively assessing its main features, airway obstruction, spontaneously reversible or after use of a bronchodilator drug, ventilation inhomogeneity during an acute bronchoconstriction and airway hyperresponsiveness. In young children that cannot cope with classical tests, it is important to use and develop simple, short lasting methods, made in spontaneous ventilation without active cooperation. Such techniques are a measurement of respiratory resistance by forced oscillations or the interrupter technique, of specific airway resistance by plethysmography and capnography. All these parameters are sensitive to the presence of an airway obstruction and to a bronchodilator or bronchoconstrictor agent, but their cutoff values in differentiating between asthmatic and healthy children as well as their specific indications in asthma management remain to be established.

Airway obstruction, upper airway artifact and response to bronchodilator in asthmatic and healthy children.

BACKGROUND: The forced oscillation technique (FOT) may be affected by the upper airway artifact in children with airway obstruction. The aim was to test the impact of the artifact on FOT ability to diagnose asthma in children as recommended by current guidelines. METHODS: The FOT was performed in 58 asthmatics and 27 controls before and after salbutamol. Respiratory resistance (Rrs) was measured at 8 Hz with a standard generator (SG), and a head generator (HG) that minimizes the upper airway artifact. The response to salbutamol was computed as change in respiratory resistance (Δ%Rrs) and admittance (Δ%Ars) that almost cancels the effect of the upper airway artifact. RESULTS: Rrs and Δ%Rrs were significantly larger in patients than controls by HG (respectively P < 0.001 and P = 0.002) but not SG, while Δ%Ars was larger in asthma than control by both (P < 0.04). Best discriminators between patients and controls were Rrs or Δ%Rrs by HG and Δ%Ars by SG. CONCLUSION: In asthmatic children, the upper airway artifact significantly impacts FOT measurements. The diagnostic value may be improved by minimization of the shunt, such as the computation of Δ%Ars.

Specific airway resistance in healthy young Vietnamese and Caucasian adults.

In healthy Vietnamese children the respiratory resistance has been suggested to be similar at 110 cm height but larger at 130 cm when compared with data in Caucasians from the literature, suggesting smaller airways in older Vietnamese children (Vu et al., 2008). The hypothesis tested here is whether the difference in airway resistance remains consistent throughout growth, and if it is larger in adult Vietnamese than in Caucasians. Airway resistance and Functional Residual Capacity were measured in healthy young Caucasian and Vietnamese adults in their respective native country using identical equipment and protocols. Ninety five subjects in Vietnam (60 males) and 101 in France (41 males) were recruited. Airway resistance was significantly larger in Vietnamese than in Caucasians and in females than in males, consistent with difference in body dimensions. Specific airway resistance however was not different by ethnicity or gender. The findings do not support the hypothesis that airway size at adult age - once normalized for lung volume - differs between Vietnamese and Caucasians.

Neonatal hyperoxia up regulates cough reflex in young rabbits.

A link between cough in childhood and neonatal exposure to hyperoxia following preterm birth has been suggested. The hypothesis is tested that neonatal exposure to hyperoxia is associated with long term up regulation of cough. Airway hyperresponsiveness is also investigated because it is a frequent finding in children born preterm and may be linked to cough. Thirty nine young rabbits survived a 48 h neonatal exposure to 93% oxygen (H, n=26) or continued room air (A, n=13). Cough response to mechanical tracheal stimulation and airway responses to a mock exercise and to methacholine were studied under anaesthesia. Larger incidence of coughs and increased sensitivity to tracheal stimulation occurred in H vs A (p<0.01), while bronchial responses to exercise or methacholine were similar in both groups. Neonatal hyperoxia is associated with up regulation of cough in young rabbits. The lack of a parallel increase in airway responsiveness suggests up regulation may be of central origin.

Flow dependence of specific airway resistance and diagnostic of asthma in children.

Panting majors turbulent flow and contribution of larger airways to the measurement of specific airway resistance (sRaw). The hypothesis was tested that the difference between asthmatic and healthy children is enhanced by narrowing the flow interval to compute sRaw. sRaw was measured during panting in 40 asthmatic and 25 healthy children and computed using all data points (full scale flow) and limited to the flow intervals ± 1L/sec and ± 0.5 L/sec. sRaw was not different between asthmatics (0.87 ± 0.20 kPa.s) and controls (0.80 ± 0.25 kPa.s) when computed full scale, while it was significantly larger in asthmatics than controls within ± 1L/sec (0.77 ± 0.16 kPa.s vs 0.65 ± 0.15 kPa.s, P < 0.004) or ± 0.5 L/sec (0.77 ± 0.21 kPa.s vs 0.61 ± 0.17 kPa.s, P < 0.002). On the other hand, the within subject coefficient of variation was significantly larger when sRaw was computed within ± 1L/sec (13.7 ± 7.2%) or ± 0.5 L/sec (28.3 ± 18.1%) than full scale (11.0 ± 6.7%), respectively P < 0.002 and P < 0.0001. It is concluded that narrowing the flow interval to compute sRaw is associated with better discrimination between asthma and health in children, although the short term variability of sRaw is increased.

Specific airway resistance in children: panting or tidal breathing?

BACKGROUND: The measurement of specific airway resistance during tidal breathing (sRaw(tb)) has gained popularity in children, but methodological concerns have been raised regarding the electronic compensation for the thermal artifact. The panting method (sRaw(p)) is efficient in minimizing the latter, but may be associated with a change in end expiratory lung volume if the effort is not properly balanced. The aim of the study was to compare sRaw(tb) with sRaw(p) in children. METHODS: Fifty-five children aged 6.5-11.5 years were studied. sRaw(tb) was measured in a commercial plethysmograph. sRaw(p) was measured with a home made equipment that allowed breath by breath analysis (sRaw(p1)) as well as with the commercial body box (sRaw(p2)). RESULTS: sRaw(tb) was significantly larger than either sRaw(p1) or sRaw(p2) (P < 0.0001). The mean (95% CI) difference sRaw(p1) - sRaw(tb) was -0.374 (-0.835 to 0.088) kPa s. The difference between sRaw(p1) and sRaw(p2) was significant (P < 0.005) but not clinically relevant, and mean (95% CI) difference sRaw(p1) - sRaw(p2) was 0.115 (-0.094 to 0.324) kPa s. The breath by breath analysis showed small but significant increase in sRaw(p1) throughout the maneuver (P < 0.001), whatever the pattern of end expiratory level. CONCLUSION: Tidal breathing is associated with an overestimation of sRaw compared with panting in children. Although the latter results in small increase throughout the panting maneuver, sRaw(p) is probably more trustful than sRaw(tb).

What is chronic cough in children?

The cough reflex is modulated throughout growth and development. Cough-but not expiration reflex-appears to be absent at birth, but increases with maturation. Thus, acute cough is the most frequent respiratory symptom during the first few years of life. Later on, the pubertal development seems to play a significant role in changing of the cough threshold during childhood and adolescence resulting in sex-related differences in cough reflex sensitivity in adulthood. Asthma is the major cause of chronic cough in children. Prolonged acute cough is usually related to the long-lasting effects of a previous viral airway infection or to the particular entity called protracted bacterial bronchitis. Cough pointers and type may orient toward specific etiologies, such as barking cough in croup or tracheomalacia, paroxystic whooping cough in Pertussis. Cough is productive in protracted bacterial bronchitis, sinusitis or bronchiectasis. Cough is usually associated with wheeze or dyspnea on exertion in asthma; however, it may be the sole symptom in cough variant asthma. Thus, pediatric cough has particularities differentiating it from adult cough, so the approach and management should be developmentally specific.

Bronchodilation induced by muscular contraction in spontaneously breathing rabbits: neural or mechanical?

The respective contribution of mechanical and neural mechanisms to the bronchodilation occurring during exercise is not fully identified in spontaneously breathing animals. The airway response to electrically induced muscular contractions (MC) was studied after vagal cold block in 9 spontaneously breathing rabbits. The forced oscillation respiratory system resistance (Rrs) was measured at vagal nerve temperatures 37°C, 8°C and 4°C. Rrs was found to decrease significantly during MC in all conditions. The occasional occurrence of a deep breath was responsible for a sudden decrease in Rrs. However, when the deep breath was absent - after vagal cooling and in some experiments at 37°C - the bronchodilation was frequently dissociated from the change in breathing pattern, most likely illustrating a neural mechanism. Altogether, while some bronchodilation may be ascribed to the mechanical stretching of the airways, Rrs decreasing with little change in breathing pattern is likely related to a reflex effect, possibly a sympathetic-borne mechanism.

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.

Neural control of airway to deep inhalation in rabbits.

Bronchodilation induced by a deep inhalation (DI) is usually attributed to the mechanical interdependence between airways and parenchyma. The aim of the study was to evaluate the contribution of neural control of the airway in the response to DI. In mechanically ventilated rabbits, cervical vagi were cooled using 2 Peltier elements. Lung resistance was measured before and up to 2 min after a DI at vagus nerve temperature = 37 °C (R(L37 °C)), 8 °C (R(L8 °C)) and 4 °C (R(L4 °C)). Measurements were performed in control conditions (Ctrl) and during infusion of methacholine (Mch). At Ctrl, R(L8 °C) and R(L4 °C) were significantly lower than R(L37 °C). After Mch, however, R(L4 °C) was not different from R(L37 °C), both being significantly higher than R(L8 °C). Vagal cold block (VCB) abolished the bronchodilation observed after the control DI and reduced its magnitude after Mch. The magnitude of bronchodilation immediately after the DI was significantly related to baseline R(L) at any vagal temperature (p < 0.001), but the renarrowing was more strongly related to baseline R(L) after VCB than at baseline. The data indicate a significant contribution of respiratory reflexes to the airway response after DI, highlight the influence of vagal control of airway wall visco-elasticity and suggests the occurrence of a moderate reflex bronchodilation in response to Mch.