Reproducibility of twitch and sniff transdiaphragmatic pressures

Twitch transdiaphragmatic pressure (Tw Pdi) measured with magnetic stimulation of the phrenic nerve is used to follow up patients and to assess the effect of clinical treatments on diaphragm function. However the reproducibility of Tw Pdi on different occasions has been little studied. We investigated 32 normal subjects, measuring Tw Pdi elicited by bilateral magnetic stimulation of the phrenic nerves on two to 14 occasions. Sniff transdiaphragmatic pressure (sniff Pdi) was also measured. The mean value of Tw Pdi and sniff Pdi were 28+/-5 and 134+/-24 cm H(2)O, respectively. The within subjects coefficient of variation was 11% for both Tw Pdi and sniff Pdi. We conclude that there is a variability of Tw Pdi and the variability of Tw Pdi is the same as that of sniff Pdi.     

Cartography of human diaphragmatic innervation: preliminary data

In humans, anatomy indicates that the phrenic nerve mainly arises from the C4 cervical root, with variable C3 and C5 contributions. How this translates into functional innervation is unknown. The diaphragm response to electrical stimulation of C3, C4 and C5 was described in three patients undergoing surgical laryngeal reinnervation with an upper phrenic root (surface chest electrodes at anterior, lateral and posterior sites; oesophageal and gastric pressures (Pes and Pga) to derive transdiaphragmatic pressure (Pdi)). Anatomically, the phrenic nerve predominantly originated from C4. Phrenic stimulation elicited motor responses at the three sites in the three patients, as did C4 stimulation. It produced Pdi values of 9, 11, and 14cmH(2)O in the three patients, respectively, vs. 9, 9, and 7cmH(2)O for C4. C3 stimulation produced modest Pdi responses, whereas C5 stimulation could produce Pdi responses close to those observed with C4 stimulation. These singular observations confirm the dominance of C4 in diaphragm innervation but suggest than C5 can be of importance.     

Diaphragmatic effects of selective resection of the upper phrenic nerve root in dogs

The aim of this study was to evaluate the effects on the diaphragm of upper phrenic nerve root resections in dogs. During laryngeal reinnervation, selective resections of the upper phrenic nerve root (C5) were performed unilaterally (right side, n=7; Group A) and bilaterally (n=6; Group B) and compared to non denervated animals (n=5). After 8 months, a diaphragmatic evaluation was performed: X-ray, EMG, transdiaphragmatic pressure (Pdi) after ipsi- and bilateral tetanic stimulation of the phrenic nerves and a bilateral histological study of five hemidiaphragmatic regions. EMG alterations were significantly more severe in Group B than in Group A, for the left (p<0.05) and right hemidiaphragms (p<0.01). No differences in the X-rays were noted between the three groups. The Pdi of the three groups after occlusion and phrenic nerve stimulations (unilateral and bilateral) were not statistically different. Histological data demonstrated that there were no differences in fibre irregularity, predominant fibre type or fibrosis between the three groups. Macroscopic and microscopic atrophy, which was mainly present on the anterior regions of the hemidiaphragms, was significantly higher in Group B than in Group A and undenervated dogs (p<0.05). In conclusion, resection of the upper phrenic nerve root of one phrenic nerve (right side) have limited effect on the diaphragm in dogs. However, resection of the upper phrenic nerve root on both sides resulted in a significant effect on the EMGs and histology of the entire diaphragm without any significant consequences on transdiaphragmatic pressure.     

Contractile properties of the human diaphragm during chronic hyperinflation

BACKGROUND. In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm. METHODS. In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion). RESULTS. At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa). CONCLUSIONS. The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.     

Controlled twitch mouth pressure reliably predicts twitch esophageal pressure

The present study hypothesized that twitch mouth pressure (TwPmo) can reliably predict intrathoracic pressure swings reflected by twitch esophageal pressure (TwPes) using a controlled and automated trigger technique. TwPmo, TwPes, and transdiaphragmatic pressure (TwPdi) following bilateral anterior magnetic phrenic nerve stimulation were measured in 21 healthy subjects using an inspiratory pressure trigger (0.5kPa, experiment 1), an expiratory pressure trigger (0.5kPa, experiment 2), an inspiratory flow trigger (40ml/s, experiment 3), and no trigger at relaxed functional residual capacity (experiment 4). TwPmo and TwPes were correlated as follows: r=0.99, p<0.0001 (experiment 1); r=0.67, p=0.001 (experiment 2); r=0.96, p<0.0001 (experiment 3); no correlation (experiment 4). Bland and Altman analysis revealed most narrow limits of agreement for TwPmo and TwPes in experiment 1: bias (range) 0.15kPa (-0.03 to 0.32). TwPmo is an excellent predictor for TwPes when using a fully automated and controlled inspiratory pressure trigger. Thus, measurement of TwPmo could become a standard means assessing inspiratory muscle strength.     

Effect of increased diaphragm activation on diaphragm power spectrum center frequency

Increased transdiaphragmatic pressure, reduced muscle blood flow, and increased duty cycle have all been associated with a reduction in the center frequency (CFdi) of the diaphragm's electrical activity (EAdi). However, the specific influence of diaphragm activation on CFdi is unknown. We evaluated whether increased diaphragm activation would result in a greater decline in the CFdi when pressure-time product (PTPdi) was kept constant. Five healthy subjects performed periods of intermittent quasi-static diaphragmatic contractions with a fixed duty cycle. In separate runs, subjects targeted transdiaphragmatic pressures (Pdi) by performing end-inspiratory holds with the glottis open and expulsive maneuvers at end-expiratory lung volume (EELV). Diaphragm activation and pressures were measured with an electrode array and balloons mounted on an esophago-gastric catheter, respectively. The EAdi, which was 25+/-8%(S.D.) of maximum at EELV, increased to 61+/-8% (P<0.001) when an identical Pdi (averaging 31+/-13 cmH2O) was generated at a higher lung volume (77% of inspiratory capacity). The latter was associated with a 17% greater decline in CFdi (P=0.012). In order to reproduce at EELV, the decrease in CFdi observed at the increased lung volume, a two-fold increase in PTPdi was required. We conclude that CFdi responds specifically to increased diaphragm activation when pressure-time product remains constant.     

Maximal activation of the human diaphragm but not inspiratory intercostal muscles during static inspiratory efforts

It is widely held that transdiaphragmatic pressure is a reliable index of the extent of central activation of the diaphragm but the maximal voluntary transdiaphragmatic pressure is lower during inspiratory than expulsive efforts. To determine whether the diaphragm is fully activated during the two manoeuvres supramaximal stimuli were delivered to both phrenic nerves during maximal efforts. No discernible twitch was evoked during 30-55% of attempted maximal efforts with either voluntary manoeuvre. Thus the difference in maximal transdiaphragmatic pressure between the manoeuvres must reflect changes in chest-wall geometry or mechanics rather than in the phrenic motor outflow. Inspiratory intercostal muscle activity was consistently submaximal during maximal inspiratory efforts.     

手工缝合肺残面施行肺减容手术治疗重度肺气肿

目的 探讨手工缝合肺残面方法肺减客手术治疗重度慢性阻塞性肺气肿的疗效。方法 本组肺减容手术20例，其中双侧肺减容6例，单侧肺减容14倒。切口的选择依据手术切除靶区的位置，其中平卧位正中切口、双侧LVRS1例，侧卧住后外侧开胸LVRS14侧，前外侧开胸LVRS11侧。术前及术后6月查肺功能（FEV1，TLC，RV）、动脉血气分析、6分钟步行距离进行对比。结果 本组无手术死亡，患者术后肺功能指标比术前有明显改善（P〈0．05），动脉血氧分压术后比术前明显提高（P〈0．05），二氧化碳分压术后比术前明显降低（P〈0．05）；呼吸困难指数再分级，15例术前3级中6例转为1级，9例转为2级；5例4级中1例转为3级，3例转为2级，1例转为1级。结论 重度肺气肿病人行肺减容手术，能改善患者肺功能，提高生活质量。     

The effect of level of contraction on the electromyographic power spectrum of the diaphragm in pigs.

We investigated the relationship between the frequency components of myoelectric power spectra of the diaphragm and the level of diaphragmatic contraction in seven anaesthetized spontaneously breathing pigs. Electromyographic activity of the costal and crural portions of the diaphragm were recorded with fish-hook electrodes and the frequency-power spectra during inspiration were computed and expressed in terms of centroid frequency (fc). Diaphragmatic force was indirectly assessed as transdiaphragmatic pressure (Pdi) which was measured with balloon-catheter systems placed in the abdomen and oesophagus. The relationships between Pdi and costal and crural fc were assessed during brief (2 min) and incremental increases in diaphragmatic contraction, achieved by gradual occlusion of the inspiratory line of the breathing circuit. When Pdi was increased to 128, 191, 287 and 421% of the value measured during unobstructed breathing, costal and crural fc rose significantly in all animals because of an increase in the power of high-frequency components and a decline in the power of low-frequency components. Both costal and crural fc returned to control values within 5 min of the release of inspiratory occlusion. Our results indicate that the level of contraction is an important determinant of the diaphragmatic myoelectric power spectrum and should be taken into consideration when using power spectral analysis to diagnose diaphragmatic mechanical failure.     

Dynamic lung mechanics in late-stage emphysema before and after lung volume reduction surgery

This study evaluated the effects of lung volume reduction surgery (LVRS) on the heterogeneity of lung function in awake, late-stage emphysema patients with measurements taken before and after full recovery from LVRS. We assessed standard clinical measures of lung function and functional heterogeneity in six awake, late-stage emphysema patients before and 6 months after LVRS. Functional heterogeneity was quantified by measuring dynamic inspiratory resistance (R(L)(insp)) and elastance (E(L)(insp)) over a frequency range that included normal breathing ( approximately 0.33-8 Hz). Since LVRS involves targeted resection of emphysematous regions of the lung, we hypothesized that emphysema patients would be functionally more homogeneous post-LVRS. We also compared our measures of functional heterogeneity with indices of anatomic heterogeneity and severity using high-resolution computed tomography (HRCT). After LVRS, 6 min walk distance increased by 22% (940+/-91 versus 1158+/-299, p=0.031) and recoil pressure at TLC increased (9.0+/-2.0 versus 14+/-5, p=0.031), but changes in R(L)(insp) and E(L)(insp) varied greatly between subjects. A measure of anatomic severity quantified using HRCT positively correlated with airway resistance (r(s)=0.89, p=0.048). These results suggest that subjects with more severe disease as assessed by HRCT criteria had reduced overall effective airway caliber consequent to active airway constriction, reduced parenchymal tethering, and/or loss of parallel lung units. Furthermore, LVRS may not necessarily improve lung function via a substantial reduction in mechanical heterogeneity.     

Combined pulmonary fibrosis and emphysema: How does cohabitation affect respiratory functions?

PurposeCombined pulmonary fibrosis and emphysema (CPFE) has emerged as a new syndrome with characteristics of both fibrosis and emphysema. We determined the impacts of radiologic emphysema severity on pulmonary function tests (PFTs), exercise capacity and mortality.Patients and methodsIPF patients (n = 110) diagnosed at the Chest Diseases Clinic between September 2013 and January 2016 were enrolled in the study and followed up until June 2017. Visual and digital emphysema scores, PFTs, pulmonary artery pressure (sPAP), 6-minute walking test, composite physiologic index (CPI), and survival status were recorded. Patients with emphysema and those with pure IPF were compared.ResultsThe CPFE-group had a significantly greater ratio of men(p < 0.001), lower BMI (p < 0.001), lower mean PaO₂ (p = 0.005), higher mean sPAP (p = 0.014), and higher exercise desaturation (p < 0.001). The CPFE group had a significantly higher FVC(L)(p = 0.016), and lower FEV1/FVC ratio (p = 0.002), DLCO, and DLCO/VA ratio(p = 0.03 and p = 0.005, respectively). Lung volumes of the CPFE group had significantly higher VC(p = 0.017), FRC (p < 0.001), RV(p < 0.001), RV/TLC(p < 0.001), and TLC(p < 0.001). There were significant correlations between emphysema scores and FVC (L)(p = 0.01), FEV1/FVC(p = 0.001), DLCO (p = 0.003), VC(p = 0.014), FRC (L)(p < 0.001), RV(p < 0.001), TLC(p < 0.001), and RV/TLC (p < 0.001). Mortality rates were comparable between the two groups. CPI (p = 0.02) and sPAP (p = 0.01) were independent predictors of mortality in patients with CPFE.ConclusionsThe presence and severity of emphysema affects pulmonary function in IPF. Patients with CPFE have reduced diffusion capacity, more severe air trapping, worse muscle weakness, more severe exercise desaturation, and pulmonary hypertension. CPI and pulmonary hypertension are two independent risk factors for mortality in subjects with CPFE.     

Diaphragm motor unit recruitment in rats

We hypothesized that considerable force reserve exists for the diaphragm muscle (DIAm) to generate transdiaphragmatic pressures (Pdi) necessary to sustain ventilation. In rats, we measured Pdi and DIAm EMG activity during different ventilatory (eupnea and hypoxia (10% O₂)–hypercapnia (5% CO₂)) and non-ventilatory (airway occlusion and sneezing induced by intranasal capsaicin) behaviors. Compared to maximum Pdi (Pdi_max generated by bilateral phrenic nerve stimulation), the Pdi generated during eupnea (21 ± 2%) and hypoxia–hypercapnia (28 ± 4%) were significantly less (p < 0.0001) than that generated during airway occlusion (63 ± 4%) and sneezing (94 ± 5%). The Pdi generated during spontaneous sighs was 62 ± 5% of Pdi_max. Relative DIAm EMG activity (root mean square [RMS] amplitude) paralleled the changes in Pdi during different ventilatory and non-ventilatory behaviors (r² = 0.78; p < 0.0001). These results support our hypothesis of a considerable force reserve for the DIAm to accomplish ventilatory behaviors. A model for DIAm motor unit recruitment predicted that ventilatory behaviors would require activation of only fatigue resistant units.     

Novel method for transdiaphragmatic pressure measurements in mice

The diaphragm muscle (DIAm) is responsible for breathing and determines the ability to generate both ventilatory and non-ventilatory behaviors. Size limitations of the mouse make transdiaphragmatic pressure (Pdi) measurement using a dual balloon system untenable. Adult C57BL/6J mice (n = 8) and C57BL/6 × 129 (n = 9), underwent Pdi measurements using solid-state pressure catheters spanning the thoracic and abdominal surfaces of the DIAm. Measurements were conducted during eupnea, hypoxia (10% O₂)–hypercapnia (5% CO₂), chemical airway stimulation (i.e., sneezing), spontaneously occurring deep breaths, sustained tracheal occlusion, and bilateral phrenic nerve stimulation. There was a difference in the Pdi generated across the range of ventilatory and non-ventilatory behaviors (p = 0.001). No difference in Pdi across behaviors was evident between mouse strains (p = 0.161). This study establishes a novel method to determine Pdi across a range of DIAm behaviors in mice that may be useful in evaluating conditions associated with reduced ability to perform expulsive, non-ventilatory behaviors.     

Functional evaluation of lung by Xe-133 lung ventilation scintigraphy before and after lung volume reduction surgery (LVRS) in patients with pulmonary emphysema

We evaluated the respiratory functions of patients with pulmonary emphysema who underwent lung volume reduction surgery (LVRS) by the mean transit time (MTT) with Xe-133 lung ventilation scintigraphy, forced expiration volume in 1 sec (FEV1.0), residual volume (RV), distance walked in 6 min (6-min walk), and the Hugh-Jones classification (H-J classification) before and after LVRS. In 69 patients with pulmonary emphysema (62 men, 7 women; age range, 47-75 years; mean age, 65.4 years +/- 6.1, preoperative H-J classification, III (two were II)-V) who underwent LVRS, all preoperative and postoperative parameters (MTT 3 weeks after LVRS and the others 3 months after LVRS) were judged statistically by the Wilcoxon signed-ranks test and Odds ratio. Every postoperative parameter was improved with a significant difference (P < 0.05) compared to preoperative parameters. MTT at 3 weeks after LVRS was not associated with %FEV1.0 and the H-J classification at 3 months after LVRS, but was associated with RV and a 6-min walk at 3 months after LVRS. MTT was useful for the clinical evalution of aerobic capability after LVRS.     

Mechanical limitation during CO2 rebreathing in young patients with cystic fibrosis

The aim of the study was to determine whether a decrease in the ventilatory response to carbon dioxide (CO2) in children with cystic fibrosis (CF) is related to a mechanical limitation of the respiratory muscle capacity. The ventilatory response during CO2 rebreathing was performed in 15 patients (mean forced expiratory volume in 1 s (FEV1): 37 +/- 21% predicted, mean arterial CO2: 41+/- 5 mmHg). The slope of the minute ventilation normalised for weight per mmHg CO2 increment correlated negatively with respiratory muscle output, assessed by the oesophageal (p = 0.002), the diaphragmatic pressure time product (p = 0.01), and the tension time index (p = 0.005). In addition, this slope was correlated with dynamic lung compliance (p < 0.0001) and FEV1 (p = 0.03) but not with airway resistance and maximal transdiaphragmatic pressure. Therefore, an excessive load imposed on the respiratory muscles explains the blunting of the ventilatory response to CO2 in young patients with CF.     

Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure

We studied the effects of hypophosphatemia on diaphragmatic function in eight patients with acute respiratory failure who were artificially ventilated. Their mean serum phosphorus level was 0.55 +/- 0.18 mmol per liter (normal value, 1.20 +/- 0.10). The contractile properties of the diaphragm were assessed by measuring the transdiaphragmatic pressure generated at functional residual capacity during bilateral supramaximal electrical stimulation of the phrenic nerves. Diaphragmatic function was evaluated in each patient before and after correction of hypophosphatemia, which was achieved by administration of 10 mmol of phosphorus (as KH2PO4) as a continuous infusion for four hours. After phosphate infusion, the mean serum phosphorus level increased significantly (1.33 +/- 0.21 mmol per liter, P less than 0.0001). The increase in serum phosphorus was accompanied by a marked increase in the transdiaphragmatic pressure after phrenic stimulation (17.25 +/- 6.5 cm H2O as compared with 9.75 +/- 3.8 before phosphate infusion, P less than 0.001). Changes in the serum phosphorus level and transdiaphragmatic pressure were well correlated (r = 0.73). These results strongly suggest that hypophosphatemia impairs the contractile properties of the diaphragm during acute respiratory failure, and they emphasize the importance of maintaining normal serum inorganic phosphate levels in such patients.     

Comparison of mouth and oesophageal pressure fluctuations during panting against an occlusion

In four normal volunteers, differences between oesophageal pressure fluctuations (delta Pes) in the upper and lower parts of the oesophagus and mouth pressure fluctuations (delta Pm), simultaneously measured during panting against an occlusion, were evaluated. Averaged quasi static pressure-volume curves were obtained by measuring pressure in the upper and lower thirds of the oesophagus. The differences between delta Pes and delta Pm during panting, due to elastic recoil changes, were predicted from an exponential relationship fitted to the pressure-volume curves. The calculated errors were compared with those observed experimentally. In the lower part of the oesophagus, delta Pes was similar to delta Pm at lung volumes in the range of 50 to 70% of Vmax. Vmax was deduced from the asymptote of the exponential curve. Mean delta Pes/delta Pm was 0.98 +/- 0.08 (SD). In the upper oesophagus, delta Pes was lower than delta Pm. Mean delta Pes/delta Pm was 0.87 in the range of 50 up to 90% of Vmax with an SD +/- 0.15. At lung volumes above 90% of Vmax for the upper oesophagus and above 70% of Vmax for the lower oesophagus, the ratio of delta Pes to delta Pm exceeded 1 and progressively increased. The measured values were often higher than those predicted from the fitted curves, presumably due to a narrowed glottic aperture. We concluded that in normals both the positioning of the oesophageal balloon in the lower oesophagus and a lung volume near functional residual capacity (FRC) are prerequisites for the use of delta Pm as a control for delta Pes, or vice versa, during panting against an occlusion.     

Glottis constriction response in healthy subjects

The purpose of this study was to evaluate the glottis constriction response induced by a sudden and involuntary increase in gastric and oesophageal pressures by Tll-Ll intervertebral magnetic stimulation of the abdominal muscle roots in nine healthy subjects. Twitch flow, twitch gastric, and oesophageal pressures were measured after abdominal muscle root stimulation, which allowed pharyngo-laryngeal muscle activation to be characterized. Pharyngeal endoscopies were performed on five subjects to assess vocal cord movements. All stimulations induced positive gastric and oesophageal pressures and expiratory flow, which increased with stimulation intensity (flow: R=0.32; p<0.0001; oesophageal pressure: R=0.26; p=0.001; gastric pressure: R=0.37; p<0.0001). Twitch gastric pressure and twitch oesophageal pressure were negatively correlated with twitch flow (respectively, R=-0.183, p<0.05; R=-0.35, p<0.0001). Upper airway resistance was higher at peak oesophageal pressure than at peak flow (p<0.001). Peak twitch gastric and twitch oesophageal pressure latencies were similar (133+/-4ms and 122+/-4ms) but longer than peak twitch flow and EMG latencies (62+/-2ms and 73+/-4ms, p<0.0001). Glottis constriction following magnetic abdominal muscle root stimulation was seen in all subjects during endoscopy, with a latency estimated at between 80 and 100ms. This method could be a new, simple tool for assessing the upper airway constriction protective reflex.     

Effects of diaphragm activation on airway pressure generation during lower thoracic spinal cord stimulation

Lower thoracic spinal cord stimulation (SCS) results in the generation of large positive airway pressures. The potential effects of diaphragm co-activation during SCS were investigated in 10 anesthetized dogs. Diaphragm compound action potentials (CMAPs) were present during SCS at the T10 and T12 levels. In group 1, airway (Paw) and trans-diaphragmatic (Pdi) pressures were monitored during supramaximal SCS before and after phrenicotomy. In group 2, pressures were monitored before and after C2 section to evaluate the potential influence of supraspinal centers. Following phrenicotomy in group 1, the reduction in Pdi during SCS was associated with increases in Paw. In group 2, diaphragm CMAPs and active Pdi increased following C2 section, while Paw fell. Following phrenicotomy, Paw increased significantly. In intact animals therefore, changes in Paw during SCS are affected by the interaction between inhibitory and excitatory influences on diaphragm activation. We conclude that lower thoracic SCS results in substantial diaphragm co-activation and secondary reductions in airway pressure generation.     

Mite avoidance can reduce air trapping and airway inflammation in allergic asthmatic children

BACKGROUND: We investigated the effects of prolonged allergen avoidance in 18 house dust mite-sensitized asthmatic children during a prolonged residential period at a high altitude, allergen-free environment. METHODS: Evaluations of residual volume (RV) and exhaled nitric oxide (eNO) were performed (i) at admission to the residential house in September, (ii) in December after 3 months of stay, (iii) in January after 15 days at home, exposed to allergens, and (iv) in June after 9 months of stay. RESULTS: During the study period RV showed a significant decrease in December (from 117.5 +/- 7.7% to 96.5 +/- 3.2%) (P < 0.02) and a following increase in January (126.2 +/- 17.2%), after allergen re-exposure (P < 0.03). RV decreased again in June at the end of the study period (91.1 +/- 6.0%) (P = 0.001). FEV(1), FEF(25-75) and VC values did not present significant variations. ENO showed a significant decrease in December after 3 months at high altitude (from 21.3 +/- 3.9 p.p.b. to 11.9 +/- 1.7 p.p.b.) (P = 0.03), but no further significant change. No correlation was found between lung volumes and eNO, probably reflecting different aspects of asthma. CONCLUSIONS: Results suggest that RV may be more sensitive than other respiratory function parameters in identifying children with air trapping, being influenced significantly as the inflammatory indices by effective allergen avoidance/exposure regimen.