Exhaled nitric oxide in symptomatic children at preschool age predicts later asthma.

BACKGROUND: Prediction of asthma in young children with respiratory symptoms is hampered by the lack of objective measures applicable in clinical routine. In this prospective study in a preschool children cohort, we assessed whether the fraction of exhaled nitric oxide (FeNO), a biomarker of airway inflammation, is associated with asthma at school age. METHODS: At baseline, IgE and eosinophils were measured in the blood, and FeNO was measured offline in 391 children aged 3-47 months with lower airway symptoms. We developed an asthma predictive index (API) including high FeNO as major criterion. At follow-up, primary outcome was physician-diagnosed asthma based on standardized interviews in those children reaching school age (n = 166). RESULTS: FeNO was significantly elevated in those children with later asthma (68/166) as compared to children not developing asthma. Median (IQR) FeNO was 10.5 (6.6-17.2) vs. 7.4 (5.3-10.3) ppb. Per 5 ppb FeNO increase, the odds ratio (95% CI) for asthma increased by 2.44 (1.61-3.70) without changing when adjusting for confounders. Using the new API, children scored at risk had 58.0% probability for later asthma, whereas the negative predictive value was 78.2%, which was comparable to the classical API. CONCLUSIONS: In this cohort of high-risk preschool children, elevated FeNO is associated with increased risk for school-age asthma. The new API including FeNO identifies children at risk of later asthma comparably to the classical API, but does not require blood sampling.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Longitudinal monitoring of pediatric cystic fibrosis lung disease using nitrite in exhaled breath condensate.

Cystic fibrosis (CF) lung disease is characterized by airway inflammation and airway infection. Nitrites in exhaled breath condensate (EBC-NO(2)(-)) have been shown to be increased in children and adults with CF compared to healthy controls suggesting its use as a measure of airway inflammation. This longitudinal study aimed to evaluate if repeated measurements of EBC-NO(2)(-) are helpful in monitoring CF lung disease activity in children. Thirty-two children with mild CF lung disease (age 10.6 +/- 3.3 years) were recruited in two study centers. Follow-up visits occurred every 3 months over a period of 1 year with a total of five visits. Each visit included a clinical assessment incorporating a modified Shwachman-Kulczycki (SK) score, spirometry, an oropharyngeal swab, or sputum sample for bacterial analysis and an EBC sample analyzed for NO(2)(-) using a spectrophotometric assay. Furthermore at the first and the last visit a chest radiograph was done and scored (Chrispin-Norman (CN) score). There was no correlation of EBC-NO(2)(-) and parameters of spirometry, SK-score, or CN-score. Furthermore, increased EBC-NO(2)(-) levels did not predict subsequent pulmonary exacerbations. We conclude that repeated measurements of EBC-NO(2)(-) are not helpful in the longitudinal monitoring of mild CF lung disease in children.

Salbutamol delivery from a hydrofluoroalkane pressurized metered-dose inhaler in pediatric ventilator circuits: an in vitro study.

STUDY OBJECTIVES: The aim of our study was to determine the in vitro delivery of salbutamol from a pressurized metered-dose inhaler (pMDI) containing hydrofluoroalkane (HFA) propellant through various delivery devices to four models of a pediatric lung. DESIGN: To determine the effect of electrostatic charge, delivery of salbutamol was initially assessed with a multistage liquid impinger (MSLI) through an inline nonchamber device (Baxter MDI Adapter) and a small (Aerochamber MV) and a large (Nebuhaler) inline chamber device. Following this, the delivery was assessed to four lung models appropriate for a child of 70 kg, 50 kg, 15 kg, and 4 kg, with the same three reduced static devices inserted directly into a pediatric ventilator circuit. MEASUREMENTS AND RESULTS: Reduction of electrostatic charge improved small particle delivery through holding chambers to the MSLI by 12 to 14%. In the ventilator model, the mean delivery was between 1.9% and 5.4% for the nonchamber device, between 14.3% and 27.2% for the small holding chamber, and between 7.2% and 25.7% for the large holding chamber. Delivery was the least efficient in the 4-kg model compared to the 70-kg, 50-kg, and 15-kg models. CONCLUSIONS: Salbutamol from an HFA pMDI is delivered efficiently through inline holding chambers with reduced static in pediatric ventilator settings. A large holding chamber has no advantage over a small holding chamber. In addition, salbutamol delivery is more efficient through a holding chamber than through a nonchamber device.

Partitioning of alterations in pulmonary mechanics due to vascular engorgement in piglets.

The aim of our study was to determine the effects of pulmonary vascular engorgement on airways and pulmonary tissues in juvenile animals before and after methacholine (Mch)-induced changes in lung function. Five anesthetized, paralyzed, and thoracotomized piglets were studied before and during pulmonary vascular engorgement, induced by inflating a left atrial balloon catheter and by calculating respiratory mechanics from measurements of airway opening (Pao) and alveolar pressures (PA), respiratory flow (V'), and volume (V) recorded during mechanical ventilation, using the multilinear regression technique. A maximal increase of 15 mmHg in pulmonary artery pressure (Ppa) resulted in a mean increase in total lung elastance (EL) of 28.6% and in total lung resistance (RL) of 14.9%. Mch increased EL by 21.7% and RL by 29.0%. Inflation of the left atrial balloon with an associated increase in Ppa by 15 mmHg in the presence of Mch resulted in an increase in EL by a further 12.4% (to 135.4% of baseline) and in RL by a further 9.0% (to 139.5% of baseline). The change in RL was associated with a qualitatively similar change in both tissue resistance (Vti) and airway resistance (Raw) before and after Mch-induced changes in lung function. We conclude that increasing pulmonary vascular pressures, by increasing left partial pressure, alters lung function in juvenile animals by altering the mechanical properties of both airways and lung tissues. The methods used in the present study allow a direct assessment of the site of action of vascular engorgement in the lungs and provide a useful model for studying this phenomenon further.

Parental attitudes toward infant pulmonary function testing.

Infant pulmonary function tests (PFTs) have proven increasingly popular and useful for clinical and research purposes. Informed consent requires accurate information on side effects. Our aim was to quantify minor side effects from a parental point of view by means of a questionnaire. The parents of 97 infants attending for PFTs were asked to complete a simple questionnaire. Eighty-one parents (84%) returned the questionnaire. Forty-one percent felt that their infants were not troubled by the process of administering the sedative chloral hydrate, whereas 55% suffered mild to moderate distress. In contrast, 94% of infants were not distressed by the actual PFTs. Similarly, 46% of parents were not distressed by the administration of sedative to their infant, with 49% expressing distress to a mild or moderate degree. Although 73% of parents were not distressed by watching their infants undergo the PFTs, 27% were to a mild to moderate degree. Seventy-three percent of infants were untroubled on waking. Seventy percent of infants had a good nights sleep after the PFTs. The vast majority of parents (94%) were happy to recommend that others allow their infants to undergo similar testing. We noted that most problems caused by infant PFTs relate to the administration of the sedative. Most infants awake from the tests not distressed and sleep normally the following night.

Bronchodilator responsiveness testing using raised volume forced expiration in recurrently wheezing infants.

We hypothesized that a new test of infant lung function, less affected by shifts in lung volume, might better detect bronchodilator effects. Using the raised volume forced expiration technique (RVFET), the effect of a bronchodilator on lung function was studied in 22 infants with a history of recurrent wheeze and five healthy infants. Forced expiratory volume in 0.75 s (FEV0.75), forced expiratory vital capacity (FVC), and forced expiratory flow at 75% of FVC (FEF75%) were measured by forcing expiration, using an inflatable jacket from a lung volume set by an inspiratory pressure of 20 cm H2O. A minimum of five measurements were made at baseline and following the administration of 500 microg of salbutamol from a metered dose inhaler via a small volume metal spacer. Changes in lung function in the group of 25 infants who received salbutamol were compared to seven infants who received placebo aerosol. No significant changes occurred in measures of lung function following salbutamol administration when compared to baseline or placebo despite a significant increase in heart rate. A shift in lung volume is unlikely the reason why infants do not demonstrate a change in forced expiration following bronchodilator administration.

High-percentage lung delivery in children from detergent-treated spacers.

Pressurized metered-dose inhalers attached to spacers are now the most common form of delivery of anti-asthma medication in children. However, no reliable data are available of how much drug reaches the lungs in children of different ages. This information is crucial, as it determines the efficacy of therapy. In this study, we present information on the amount of drug reaching the lungs in children from a pressurized metered-dose inhaler attached to a detergent-coated spacer. We studied 18 asthmatic children inhaling radiolabeled salbutamol through detergent treated spacers to minimize electrostatic charge on the spacer wall. Lung deposition was much higher than expected when using detergent-coated spacers. Mean (SD) lung deposition, expressed as a percentage of the total actuated dose (five actuations), was 16.4% (5.5) in younger children inhaling through a small volume spacer, and 28.2% (6.7) and 41.8% (3. 8) in older children inhaling with different breathing patterns through a large volume spacer. These findings have major implications for dosage regimens for inhaled anti-asthma medication in children. Lower doses may be sufficient for adequate drugs delivered through spacers treated for static to achieve a desired clinical response.

Atypical mycobacterial pulmonary disease and bronchial obstruction in HIV-negative children.

Atypical mycobacterial infection in HIV-negative children usually presents with cervical lymphadenopathy. We report on 10 children who are HIV-negative and who presented with pulmonary disease, in whom either culture-proven atypical mycobacterium infection (four), positive avian Mantoux test (five), or lack of response to human tuberculosis treatment (one) had been observed. One case was subsequently diagnosed as chronic granulomatous disease and illustrates that children with atypical mycobacterial pulmonary infection should have their immune status fully investigated. Bronchial obstruction was observed in eight cases, and of these, endobronchial disease was found in six children. The diagnosis of atypical mycobacterial disease is difficult, and a negative avian Mantoux test does not exclude the diagnosis. The availability of clarithromycin and rifabutin has offered new therapeutic options in treating atypical mycobacterial pulmonary infection, but management of these cases can be prolonged and difficult.

Aerosol delivery to wheezy infants: a comparison between a nebulizer and two small volume spacers.

Inhalation therapy for wheezy infants with either a nebulizer or a pressurized metered-dose inhaler (pMDI) through a spacer is common practice. The aim of our study was to compare aerosol delivery to wheezy infants from a nebulizer and from a pMDI via two small volume spacers. Twenty wheezy infants (aged 4-12 months) were recruited. They inhaled salbutamol from a Pari-Baby nebulizer, from a detergent-coated Babyhaler, and from a Nebuchamber in random order. A filter was placed between the inhalation systems and the patients. The amount of salbutamol deposited on the filter was measured using an ultraviolet spectrophotometer and was expressed as a percentage of the total nebulized or actuated doses. The mean total nebulized dose for the Pari-Baby (1030 micrograms) was higher (P < 0.001) than the mean actuated dose from a pMDI for the Babyhaler (374 micrograms) and for the Nebuchamber (378 micrograms). Mean drug deposition on the filter was 40.2% (150 micrograms) of the total actuated dose for the detergent-coated Babyhaler and 40.7% (154 micrograms) of the total actuated dose for the Nebuchamber. There was no significant difference in drug deposition on the filter between the two spacers. Mean drug deposition on the filter was 25.3% (260 micrograms) of the total nebulized dose for the Pari-Baby nebulizer. There was no weight dependence in drug deposition on the filter for the two spacers, but, drug deposition increased with the subject's weight for the nebulizer. We have shown that aerosol delivery to wheezy infants from a pMDI through small volume spacers is effective and that a higher percentage of the total amount of salbutamol is delivered than from a nebulizer. The weight dependence in drug deposition for the nebulizer can be of clinical relevance.

Factors affecting the efficiency of aerosol therapy with pressurised metered-dose inhalers through plastic spacers.

AIM: The main objective of this study was to compare the in vitro delivery of salbutamol from a chlorofluorocarbon(CFC)-propelled pressurised metered-dose inhaler (pMDI) versus a newly developed hydrofluoroalkane(HFA)-propelled pMDI through various spacers. In addition, we aimed to study the effect on bronchodilator response when using an optimal pMDI/spacer combination for aerosol delivery compared to a suboptimal combination. METHODS: Particle size distribution and output from salbutamol pMDIs containing either CFC propellants (Ventolin) or HFA propellants (Airomir) were measured using a multistage liquid impinger (MSLI) and compared to that through both detergent-coated (non-static) or untreated (static) large volume (Nebuhaler, Volumatic) and small volume (Aerochamber) plastic spacers. Flow-volume curves (FEV1) were obtained from twelve asthmatic children with known significant bronchodilator response (8 males), aged 13-17 years, randomly inhaling salbutamol from a CFC-pMDI through a static spacer (Nebuhaler) and from an HFA-pMDI through a non-static spacer (Nebuhaler). RESULTS: In vitro output of particles in the respirable range (< 6.8 microns) from HFA-pMDIs was significantly higher than that from CFC-pMDIs using various spacers. Removal of electrostatic charge increased output from CFC- and HFA-pMDIs through all spacers by 17-82%. The mean (SD) bronchodilator response after inhalation of salbutamol from a CFC-pMDI through a static spacer was 7.1% (6.3%) compared to 17.5% (7.9%) after inhalation from an HFA-pMDI through a non-static spacer (p = 0.002). CONCLUSIONS: Use of a newly developed HFA-propelled pMDI greatly improves drug delivery through spacers compared to a CFC-propelled pMDI. However, electrostatic charge in plastic spacers remains the key determinant limiting delivery of salbutamol from a pMDI through spacers, and can be reduced by soaking the spacer in a household detergent. Using an optimal pMDI/spacer combination leads to a significantly improved bronchodilator response.

Wearing a noseclip improves nebulised aerosol delivery.

OBJECTIVE: The efficiency of nebulised aerosol delivery is limited due to drug retained within the nebuliser, and due to a poor ratio between inspiratory drug delivery and expiratory drug loss. Several technical approaches have improved the ratio between inspiratory aerosol delivery and expiratory aerosol loss. In our pilot study we aimed to investigate if wearing a noseclip during inhalation therapy improves the inspiratory versus expiratory ratio and hence, improves nebulised aerosol delivery. METHODS: Drug delivery was measured in thirteen subjects (7 males; age range 23-36 years) inhaling in random order nebulised aerosol through a mouthpiece once while wearing a noseclip and once without. RESULTS: Wearing a noseclip leads to an increase of 113% (SEM 23.5) in drug delivery and improves the inspiratory versus expiratory ratio (ratio 2.07 versus 0.75). CONCLUSIONS: We have shown that aerosol delivery is increased due to an improved inspiratory versus expiratory ratio when wearing a noseclip.

[Intermittent or persistent rhinitis in children and adolescents with Asthma: «the Swiss LARA paediatrics survey¼]. / Intermittierende oder Persistierende Rhinitis bei Kindern und Jugendlichen mit Asthma: «The Swiss LARA paediatrics survey¼

Asthma and allergic rhinitis are chronic inflammatory airway diseases which often occur concomitantly. The objective of the LARA program was to identify the comorbidities and characteristics of asthma (A), intermittent or persistent rhinitis (IPR) and physician defined atopic dermatitis (AD) in 6- to 16-year old asthmatic Swiss children and adolescents. Overall, 126 general practitioners and paediatricians collected the data of 670 asthmatics. Approximately one third of the asthmatic children in Switzerland had well-controlled asthma. Almost two thirds of these asthmatics suffered from concomitant IPR. The latter presented with significantly less symptoms while the treatment rates with inhaled corticosteroids (approximately 90%) and leukotriene-receptorantagonists (approximately 50%) were comparable. However, there were almost twice as many passive smokers in the less well-controlled group. The prevalence of AD was similar in both groups. IPR and AD may play an important role as risk factors in the future development of asthma.

Predictors of asthma control in everyday clinical practice in Switzerland.

OBJECTIVE: To identify predictors of improved asthma control under conditions of everyday practice in Switzerland. RESEARCH DESIGN AND METHODS: A subgroup of 1380 patients with initially inadequately controlled asthma was defined from a cohort of 1893 asthmatic patients (mean age 45.3 + or - 19.2 years) recruited by 281 office-based physicians who participated in a previously-conducted asthma control survey in Switzerland. Multiple regression techniques were used to identify predictors of improved asthma control, defined as an absolute decrease of 0.5 points or more in the Asthma Control Questionnaire between the baseline (V1) and follow-up visit (V2). RESULTS: Asthma control between V1 and V2 improved in 85.7%. Add-on treatment with montelukast was reported in 82.9% of the patients. Patients with worse asthma control at V1 and patients with good self-reported adherence to therapy had significantly higher chances of improved asthma control (OR = 1.24 and 1.73, 95% CI 1.18-1.29 and 1.20-2.50, respectively). Compared to adding montelukast and continuing the same inhaled corticosteroid/fixed combination (ICS/FC) dose, the addition of montelukast to an increased ICS/FC dose yielded a 4 times higher chance of improved asthma control (OR = 3.84, 95% CI 1.58-9.29). Significantly, withholding montelukast halved the probability of achieving improved asthma control (OR = 0.51, 95% CI = 0.33-078). The probability of improved asthma control was almost 5 times lower among patients in whom FEV(1) was measured compared to those in whom it was not (OR = 0.23, 95% CI = 0.09-0.55). Patients with severe persistent asthma also had a significantly lower probability of improved control (OR = 0.15, 95% CI = 0.07-0.32), as did older patients (OR = 0.98, 95% CI = 0.97-0.99). Subgroup analyses which excluded patients whose asthma may have been misdiagnosed and might in reality have been chronic obstructive pulmonary disease (COPD) showed comparable results. CONCLUSIONS: Under conditions of everyday clinical practice, the addition of montelukast to ICS/FC and good adherence to therapy increased the likelihood of achieving better asthma control at the follow-up visit, while older age and more severe asthma significantly decreased it.

Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis.

BACKGROUND: This is the first study to measure inducible nitric oxide synthase (iNOS) gene and protein expression quantitatively in primary epithelial cells from very young children with cystic fibrosis (CF). Low levels of exhaled nitric oxide (NO) in CF suggest dysregulation of NO production in the airway. Due to the importance of NO in cell homeostasis and innate immunity, any defect in the pathway associated with CF would be a potential target for treatment. METHODS: Cells were obtained by tracheobronchial brushing from 40 children with CF of mean (SD) age 2.1 (1.5) years and from 12 healthy non-atopic children aged 3.4 (1.2) years. Expression of iNOS mRNA was measured using quantitative PCR and iNOS protein by immunofluorescence and Western blot analysis. RESULTS: Inducible NOS mRNA expression was significantly lower in CF patients with and without bacterial infection than in healthy children (0.22 and 0.23 v 0.76; p=0.002 and p=0.01, respectively). Low levels of iNOS gene expression were accompanied by low levels of iNOS protein expression as detected by Western blot analysis. CONCLUSIONS: These results support the findings of previous studies in adult patients with advanced disease, cell lines, and animal models. Our findings reflect the situation in children with mild lung disease. They indicate that low iNOS expression may be an innate defect in CF with potential consequences for local antimicrobial defence and epithelial cell function and provide evidence for an approach to treatment based on increasing epithelial NO production or the sensitivity of NO dependent cellular processes.

The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma.

Effective treatment of respiratory symptoms, airway inflammation and impairment of lung function is the goal of any asthma therapy. Although montelukast has been shown to be a possible add-on therapy for anti-inflammatory treatment in older children, its efficacy in infants and young children is not well known. The aim of this study was to investigate its effect in infants and young children with early childhood asthma. In a prospective randomised double-blind placebo-controlled study, 24 young children (10-26 months) with wheeze, allergy and a positive family history of asthma consistent with the diagnosis of early childhood asthma were randomised to receive montelukast 4 mg or placebo. The forced expiratory volume in 0.5 seconds (FEV0.5) was measured using the raised volume rapid thoracic compression technique, and fractional exhaled nitric oxide (FeNO) and symptom scores were determined. No change was noted in FEV0.5, FeNO or symptom score in the placebo group following the treatment period. In contrast, significant improvements in mean+/-SD FEV0.5 (189.0+/-37.8 and 214.4+/-44.9 mL before and after treatment, respectively), FeNO (29.8+/-10.0 and 19.0+/-8.5 ppb) and median symptom score (5.5 and 1.5) were noted following treatment with montelukast. In conclusion, montelukast has a positive effect on lung function, airway inflammation and symptom scores in very young children with early childhood asthma.

[Aerosol therapy]. / Aerosoltherapie.

Aerosol therapy plays a major role in the diagnosis and treatment of various lung diseases. The aim of inhalation therapy is to deposit a reproducible and adequate dose of a specific drug to the airways, in order to achieve a high, local, clinical effect while avoiding serious systemic side effects. To achieve this goal, it is therefore important to have an efficient inhalation device to deliver different medications. However, the currently available therapeutic inhalation devices (nebuliser, pressurised metered-dose inhaler and dry powder inhaler) are not very efficient in aerosol delivery and have several disadvantages. Inhalation devices can be assessed by in vitro studies, filter studies and radiolabelled deposition studies. Several radiolabelled deposition studies have shown that nebulisers and pressurised metered-dose inhalers are not very efficient in aerosol delivery. In children, before 1997, only 0.5% to 15% of the total nebulised or actuated dose from a nebuliser or pressurised metered-dose inhaler actually reached the lungs. These numbers were somewhat improved in adults, 30% of the total nebulised or actuated dose reaching the airways. Aerosol therapy with dry powder inhalers was the most efficient before 1997, 30% of the total dose being deposited in the lungs of adults and children. In 1997, new developments in pressurised metered-dose inhalers much improved their efficiency in aerosol delivery. Lung deposition can be increased by up to 60% with use of a non-electrostatic holding chamber and/or a pressurised metered-dose inhaler with a hydrofluoroalkane propellant possessing superior aerosol characteristics. Several studies comparing the clinical efficiency of different inhalation devices have shown that the choice of an optimal inhalation device is crucial. In addition to the aerosol characteristics, ventilation parameters and airway morphology have an important bearing on deposition patterns. These parameters may be greatly influenced by the patient's acceptance of a specific inhalation device and therefore determine the choice of the device used. It is important for the clinical impact to develop more efficient inhalation devices, which need to be assessed for use in different age groups. These devices should be cheap, easy to use, portable, usable with all medications and environmentally safe.

Dosage regimens for inhaled therapy in children should be reconsidered.

In current asthma guidelines, dosage regimens for inhalation therapy in children are based on adult doses and are generally titrated per kilogram of bodyweight or per square metre of body surface area. However, these recommendations do not correspond well with current knowledge of aerosol therapy in childhood. Lung deposition of the aerosolised drug is the key determinant for clinical efficacy and for systemic side effects of inhalation therapy. Lung deposition increases with age, whereas lung deposition expressed as a percentage per kilogram bodyweight is age-independent. This finding is explained by the self-regulating effect of age-dependent airway anatomy on lung deposition. Therefore, it is more likely that adult doses translate into paediatric doses only by virtue of the differences in self-limiting pulmonary deposition when using the same absolute nominal doses of the medication. Adapting the adult dose to a paediatric dose calculated on body size might be unnecessary and could lead to insufficient pulmonary deposition of medication. These findings suggest that dosage regimens for inhalation therapy for children may have to be reconsidered, and should be determined from dose-ranging studies rather than calculated from adult doses based on body size.

Prevention of methacholine-induced changes in respiratory mechanics in piglets: a comparison of sevoflurane and halothane.

BACKGROUND: Sevoflurane is a new volatile anesthetic agent that may be a useful alternative to halothane for anesthesia in children. However, there is insufficient information about its effects on respiratory mechanics, particularly in the presence of constrictor stimuli. METHODS: Eighteen piglets had anesthesia induced and maintained with either pentobarbital (control: n = 8), 1 minimum alveolar concentration (MAC) sevoflurane (sevo: n = 5), or 1 MAC halothane (halo: n = 5). Pressure, flow, and volume were measured at the airway opening and used to calculate lung compliance (C(L)) and resistance (R(L)). Resistance was partitioned into airway (Raw) and parenchymal (Vti) components using alveolar pressure. Methacholine was infused intravenously in a dose sufficient (15 microg x kg(-1) x h(-1)) to approximately double R(L). RESULTS: The increase in R(L) seen in the control group was almost entirely due to an increase in Vti. Sevoflurane and halothane prevented the increase in R(L) and Vti (both P < 0.02) and the decrease in C(L) (both P < 0.02). CONCLUSIONS: Sevoflurane and halothane can prevent methacholine-induced changes in lung function.