What is the role of tests of lung function in the management of infants with lung disease?

This review considers whether there is a role for lung function tests in the clinical management of infants with lung disease. The purpose of testing lung function in older subjects, the tests available for infants, and the practical problems of testing lung function in infants are considered. After reviewing all the facts, we suggest that there are four situations in which lung function testing should be recommended for infants, as follows: (1) the infant who presents with unexplained tachypnea, hypoxia, cough, or respiratory distress in whom a definitive diagnosis is not apparent from physical examination and other, less difficult investigations; (2) the infant with severe, continuous, chronic obstructive lung disease who does not respond to an adequate clinical trial of combined corticosteroid and bronchodilator therapy; (3) the infant with known respiratory disease of uncertain severity in whom there is need to justify management decisions; and (4) research and development. A review of 62 recent publications to determine how lung function tests are being used at the present time showed that they are being used overwhelmingly for research. The role of lung function testing in the clinical management of infants has not been established, and research is needed to clarify this situation. We suggest that such studies should explore the role of lung function tests in infants with specific symptoms, signs, or diagnoses, taking into account information from other types of investigation and the cost/benefit/risk ratios.

Exhaled nitric oxide and asthma in young children.

Exhaled nitric oxide (eNO) has been used to diagnose asthma in adults and children using either the slow vital capacity method (SVCm) or, in younger children, the tidal breathing method (TBm). Adenosine 5'-monophosphate (AMP) challenge also has been found to be a sensitive and specific test for the diagnosis of asthma. In the present study, we used the AMP provocation concentration that caused wheezing (PCW) to confirm the diagnosis of asthma (PCW < or = 200 mg/mL). We studied 36 children (2-7 years) with mild intermittent asthma, 13 children (3-7 years) with moderate persistent asthma treated with inhaled steroids, 20 nonasthmatic children (2-7 years) with chronic cough and recurrent pneumonia, and 15 healthy children (4-6 years). Expired gas was collected in collection bags by the TBm, and eNO was measured. We evaluated the efficacy of eNO values in diagnosing asthma. The mean eNO level of the mild intermittent asthmatic children (5.6 +/- 0.4 ppb) not receiving inhaled corticosteroids was significantly higher (ANOVA P < 0.0001) than that of the moderate persistent asthmatics who were treated with inhaled steroids, the nonasthmatic children with chronic cough, and the group of healthy children (3.7 +/- 0.6 ppb, P < 0.05; 3.2 +/- 0.3 ppb, P < 0.001; 2.2 +/- 0.2 ppb, P < 0.001, respectively). The points of intersection for sensitivity and specificity curves of eNO to differentiate mild intermittent asthmatics from nonasthmatic children with chronic cough and from healthy children were 77% and 88% for eNO values of 3.8 ppb and 2.9 ppb, respectively. We conclude that eNO collected by the TBm can differentiate steroid-naive young children with intermittent asthma from healthy children, from nonasthmatic children with chronic cough, and from asthmatic children treated with inhaled steroids.

Can peak expiratory flow measurements estimate small airway function in asthmatic children?

BACKGROUND: Asthma is characterized in part by small airways dysfunction. Peak expiratory flow (PEF) measurement has been suggested by all international guidelines as an important tool in asthma management. The correlation between PEF and FEV(1) but not with forced expired flow at 50% of vital capacity (FEF(50)) is well-established. STUDY OBJECTIVE: To determine the value of PEF measurement as a predictor of small airways status as expressed by FEF(50). DESIGN: Analysis of the association between PEF and FEF(50) in single and multiple determinations. PATIENTS: One hundred eleven asthmatic children (mean age, 11.8 years), grouped in the following way according to FEV(1) values: within normal range (n = 46); mildly reduced FEV(1) (n = 44); and moderately/severely reduced FEV(1) (n = 21). RESULTS: Overall, FEF(50) and PEF were significantly correlated (r = 0.49; p < 0.0001). However, in 41.6% of the patients, the actual FEF(50) differed by > 20% from the calculated FEF(50). PEF has a high specificity (82.4%) but a poor sensitivity (51.7%) to detect FEF(50) status. PEF was better able to reflect abnormal FEF(50) in the patients with more severe asthma and to reflect normal FEF(50) values in the healthier patients. In patients with multiple measurements (n = 40), the correlation between FEF(50) and PEF was significantly better than that derived from a single determination (multiple measurements r = 0.77; single measurement, r = 0.49). CONCLUSIONS: Although PEF is an important tool in the management of asthmatic patients, it does not yield a complete picture because it is not sensitive in detecting small airways function. It is best used at home along with regular spirometry measurements at the clinic. PEF may serve as a better index of changes in small airways function once an individual regression is determined.

Plethysmographic measurements of lung volume and airway resistance. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/ American Thoracic Society.

Functional residual capacity (FRC) is the only static lung volume that can be measured routinely in infants. It is important for interpreting volume-dependent pulmonary mechanics such as airway resistance or forced expiratory flows, and for defining normal lung growth. Despite requiring complex equipment, the plethysmographic method for measuring FRC is very simple to apply and, unlike the gas dilution techniques, enables repeat measures of lung volume to be obtained within a few minutes. This method has the further advantage that with suitable adaptations to the equipment, simultaneous measurements of airway resistance can also be obtained. The aim of this paper is to provide recommendations pertaining to equipment requirements, study procedures and reporting of data for plethysmographic measurements in infants. Implementation of these recommendations should help to ensure that such measurements are as accurate as possible and that meaningful comparisons can be made between data collected in different centres or with different equipment. These guidelines cover numerous aspects including terminology and definitions, equipment, data acquisition and analysis and reporting of results and also highlight areas where further research is needed before consensus can be reached.

Methacholine inhalation challenge: a shorter, cheaper and safe approach.

Increased nonspecific bronchial hyperresponsiveness to pharmacological agents such as histamine or methacholine (MCh) is a hallmark of asthma. The measurement of airway reactivity is quite sensitive but testing is tedious, and time and money consuming. The present aim was, therefore, to design the shortest possible, yet safe inhalation challenge protocol applicable for a lung function referral centre. All records of studies performed in our institution during 1996 were analyzed retrospectively with a baseline ratio (bl) of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) > or = 0.7 (n=449). It was questioned what the initial dose should be, and whether some inhalation steps could have been skipped without losing pertinent information and/or causing an adverse response (a fall in FEV1 >40%). When unavailable, provocative dose causing a 20% fall in FEV1 (PD20) values were obtained by linear inter- or extrapolation of the existing data. The present study showed that three-fold concentration steps could have been employed with minimal change in outcome. Only 151449 patients (3.3%) would have experienced a severe response. Five subjects (of 169, 3.0%) with FEV1/FVCbl 0.7-0.8 reacted to inhalation up to 0.073 micromol. Four subjects (of 280, 1.4%) with FEV1/ FVCbl> or =0.8 reacted to inhalation up to 0.219 micromol. The authors suggest that: 1) an initial dose of 0.219 micromol (initial concentration= 0.21 mg.mL(-1)) may be used when the baseline ratio of forced expiratory volume in one second to forced vital capacity > or =0.8 and 0.073 micromol (initial concentration=0.07 mg.mL(-1)) when the baseline ratio is <0.8; 2) a tripling dose protocol is easier to perform, cheaper and 30.2%, faster, yet just as safe; and 3) other abbreviated protocols used in epidemiologic settings may not be applicable in a referral centre setting.

Urbanization and the risk of asthma among schoolchildren in the Palestinian Authority.

The aim of the present survey was to compare the prevalence of symptoms suggestive of asthma in boys and girls aged 6-7 and 13-14 years in a rural and an urban area in the West Bank. For this purpose, the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was issued to 970 schoolchildren in the two regions. The response rate was 92.2%. The prevalences of ever wheezing in the urban and rural areas were 16.4% and 12.0%, respectively (p < 0.05); the 12-month prevalences of wheezing were 10.5% and 5.5%, respectively (p < 0.05); the prevalences of more severe wheeze were 4.5% and 1.7%, respectively (p < 0.05); and prevalences of diagnosed asthma were 4.2% and 2.8%, respectively (p = NS). When controlling for age by stratification, the significant association between prevalence rates and place of residence persisted in the 13-14-year age group. These results also show that the prevalence of asthma among Palestinian children is moderately high in comparison with that reported from developing countries, but lower than those reported from Western countries. This survey, the first epidemiological survey on asthma in the West Bank, demonstrates a marked difference between urban and rural areas. The findings emphasize the need for further study of the environmental determinants of the disease among Palestinian children.

Cut-off points defining normal and asthmatic bronchial reactivity to exercise and inhalation challenges in children and young adults.

An analysis was undertaken to determine the optimal cut-off separating an asthmatic from a normal response to a bronchial provocation challenge by exercise and the inhalation of methacholine or histamine in children and young adults. Data were extracted, after appropriate correction, from published studies available in Medline of large random populations that complied with preset criteria of suitability for analysis, and the distribution of bronchial reactivity in the healthy population for exercise and inhalation challenges were derived. Studies on the response to exercise and methacholine inhalation in 232 young asthmatics of varying severity were carried out by the authors and the distribution of bronchial reactivity of a young asthmatic population obtained. Comparisons of the sensitivity and specificity of the challenges were aided by the construction of receiver operating characteristic curves. The optimal cut-off point of the fall in forced expiratory volume in one second (FEV1) after exercise was 13%, with a sensitivity (power) of 63% and specificity of 94%. For inhalation challenges, the optimal cut-off point for the dose of methacholine or histamine causing a 20% fall in FEV1 was 6.6 micromol, with a sensitivity of 92% and a specificity of 89%. The cut-off values were not materially affected by the severity of the asthma and provide objective data with which to evaluate the results of bronchial provocation challenges in children and young adults.

Rehabilitation of hypoxemic patients with COPD at low altitude at the Dead Sea, the lowest place on earth.

BACKGROUND: In patients with COPD, oxygen therapy has been shown to improve exercise capacity and survival. Increase in barometric pressure at low altitude can serve as a simple way to improve arterial oxygenation in hypoxemic patients. We have tried to evaluate the effect of staying at low altitude on arterial oxygenation and exercise performance in patients with COPD. PATIENTS AND METHOD: Eleven patients with COPD (9 male, 2 female) aged 38 to 79 years (mean FEV1, 0.96 L; 36% predicted) with hypoxemia (mean PaO2, 54.2+/-8.9 mm Hg) at Jerusalem (altitude 800 m above sea level) were taken down to the Dead Sea area (altitude 402 m below sea level) for 3 weeks. At both locations we tested arterial blood gases, spirometry, progressive exercise, 6-minute walking distance, and sleep oximetry. The study was repeated 2 weeks after returning to Jerusalem. RESULTS: Spirometry results were unchanged. Mean arterial PaO2 rose from 54.2+/-8.9 mm Hg to 69.5+/-11 at the first week and to 66.6+/-11 at the third week of stay (p<0.001). PaCO2 rose from 43.5+/-9.8 mm Hg to 47.7+/-9 and 49.5+/-8.4 (p<0.006). Six-minute walking distance rose from 337+/-107 m to 449+/-73 and 507+/-91 in the third week (p<0.005). Maximum oxygen consumption (VO2max) rose from 901+/-257 mL/min to 1,099+/-255 and 1,063+/-250 mL/min (p=0.01). Sleep oximetry showed an increase in mean sleep arterial oxygen saturation from 86.0+/-4.3% to 89.9+/-4.2% and 88.3+/-3.0 at 1 and 3 weeks, respectively (p<0.05). Following the return to Jerusalem, arterial gases returned to their baseline levels (PaO2, 52.9+/-9.4 mm Hg) but 6-min walking distance remained significantly high, 453+/-47 (p<0.02), and VO2max remained high as well (1,102+/-357 mL/min), although it did not reach statistical significance. CONCLUSIONS: Decline to low altitude or staving at high oxygen environment improves arterial oxygenation and exercise capacity in hypoxemic patients residing in moderate or high altitude. Low altitude (or pressurized wards) can improve pulmonary rehabilitation of hypoxemic patients with COPD.

Comparison of respiratory inductance plethysmography with thoracoabdominal compression in bronchial challenges in infants and young children.

Respiratory inductance plethysmography measuring thoracoabdominal asynchrony (TAA) has been claimed to be a useful tool for measuring changes in airway resistance in infants. In this study we evaluated the response to methacholine by thoracoabdominal compression and respiratory inductance plethysmography. Seventeen infants (mean age, 13.1 +/- 4.7 mo) with recurrent episodes of cough or wheeze underwent bronchial challenge with inhaled methacholine. Lung function was evaluated by measuring maximal expiratory flow at resting lung volume (VmaxFRC), and the degree of TAA was measured by phase angle (theta). Methacholine was inhaled for 1 min during tidal breathing using increasing doubling concentrations until a fall of at least 40% in VmaxFRC was achieved (final concentration). All infants responded to the final concentration of methacholine by a significant fall in VmaxFRC (from 31 +/- 10 to 12 +/- 5 ml/s/kg, p < 0.001). All but one infant responded to methacholine at the final concentration with a significant increase in phase angle (median theta increased from 11.7 to 31.7 degrees, p < 0.001). In two other infants there was an early response in theta compared with the response in VmaxFRC. Phase angle increase after methacholine was expressed as Z-scores (the difference between postmethacholine theta and postbuffer theta divided by the standard deviation of postbuffer theta). An increase of at least 2.0 Z-scores in theta was observed at the same concentration of methacholine when VmaxFRC fell by at least 40% in 15 of the 17 infants (88%). We conclude that respiratory inductance plethysmography is a sensitive method to measure bronchial reactivity to methacholine in most of the infants studied (14 of 17, 82%). A concentration of methacholine causing an increase in theta of at least 2.0 standard deviations above baseline is equivalent to the concentration causing a 40% fall in VmaxFRC.

Home recording of PEF in young asthmatics: does it contribute to management?

The value of home monitoring of peak expiratory flow (PEF) as part of an action plan for asthma management in children and young adults is uncertain. We sought to determine whether home recording of PEF benefited asthma management and whether any contribution was affected by the severity of the asthma. Twenty-eight children and young adults with asthma of different severity (mean age 14 yrs; 95% confidence interval (95% CI) 12-16 yrs) recorded their symptoms, drug consumption and PEF twice daily for a mean of 82 days over a 12 week period, and attended the laboratory every 2 weeks for measurement of lung function. The number of individual patients with significant correlations for laboratory lung function tests compared with ambulatory PEF and diary scores averaged over the preceeding 2 weeks was low in all severity groups. When measured in the laboratory, PEF meter readings correlated poorly with PEF measured by spirometry. The proportion of patients with significant correlations for PEF, symptoms and rescue bronchodilator use on a day-to-day basis was 70-80% in the group of severe asthmatics and significantly less in the mild asthmatics. In a subgroup of 14 patients who were sick on a mean of 19 days, the mean difference in PEF between well and sick days was 14% of predicted. Diurnal PEF variation correlated poorly with other parameters in all groups. It is concluded that PEF monitoring adds little to daily recording of symptoms and bronchodilator use in the management of young patients with severe asthma, and it is too insensitive to register meaningful clinical changes in those with milder asthma.

Adenosine, methacholine, and exercise challenges in children with asthma or paediatric chronic obstructive pulmonary disease.

BACKGROUND: Bronchial hyperreactivity to methacholine is present in children with asthma and other types of paediatric chronic obstructive pulmonary disease (COPD), while hyperreactivity to exercise is more specific for asthma. Adenosine 5'-monophosphate (AMP) is a potent bronchoconstrictor and, like exercise, may provoke asthma by activating mast cells. This study investigated the suitability of AMP as a specific challenge for asthma in children. METHODS: Bronchial provocation challenges with methacholine and AMP were performed in a double blind fashion using tidal breathing in 51 children with asthma, 21 with paediatric COPD of various types, and in 19 control children. Each subject also underwent a standardised exercise challenge after inhalation challenges were completed. Sensitivity and specificity curves were constructed and the intersection point of sensitivity and specificity for each type of challenge was determined. RESULTS: When the asthmatic patients were compared with the children with COPD, the intersection points for AMP, exercise and methacholine were 90%, 85%, and 50%, respectively. When compared with the controls the same intersection points were 98%, 84%, and 92%, and when children with paediatric COPD were compared with controls they were 55%, 50%, and 82%. CONCLUSIONS: Methacholine distinguishes both asthma and paediatric COPD from controls with a sensitivity of 82-92%, but does not distinguish between asthma and paediatric COPD; exercise and AMP distinguish asthma from controls with a sensitivity and specificity of 84-98% but they also distinguish asthma from paediatric COPD with a sensitivity and specificity of 85-90%. AMP inhalation is a practical aid for diagnosing asthma and distinguishing it from COPD in children of all ages.

Functional residual capacity (FRC) measurements by plethysmography and helium dilution in normal infants.

Comparative measurements of functional residual capacity (FRC) made by plethysmography (FRCpleth) and by helium dilution (FRCHe) were obtained on 27 infants and young children without known pulmonary disease (14 males, 13 females; 4 weeks-26 months; mean age 32.2 weeks) while under chloral hydrate sedation. Clinical histories, clinical examinations, and pulmonary functions were normal for all members of the group. FRCpleth, whether measured near end expiration (EE) or near end inspiration (EI), and corrected to mean expiratory levels of at least 3 breathing cycles, was consistently and significantly greater than FRCHe. Comparative values for mean (+/- standard deviation) were FRCpleth EE, 182.0 (+/- 79.7) mL and FRCpleth El, 171.8 (+/- 77.4) mL vs. FRCHe, 154 (+/- 72.2) mL, P < 0.0001 and P < 0.005, respectively. Normalizing values by weight, FRCpleth EE was 23.8 mL/kg (+/- 5.3) vs. FRCHe, 20.2 (+/- 4.7) mL/kg, mean (+/- standard deviation). The difference between FRCpleth and FRCHe, expressed as FRCpleth - FRCHe/FRCpleth x 100, was 9% for occlusions at end inspiration and 16% for occlusions at end expiration. The following equations describe our FRC results in relation to length: In (FRCHe) = 2.74 x ln (length) - 6.53 r2 = 0.781 slope = 2.74 +/- 0.29 SE Y intercept = 6.53 +/- 1.12 SE ln (FRCPleth EI) = 2.69 x ln (length) - 6.21 r2 = 0.752 slope = 2.69 +/- 0.31 SE Y intercept = 6.21 +/- 1.29 SE The difference between FRCpleth and FRCHe was more marked when occlusions were performed at end expiration than at end inspiration.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of natural oxygen enrichment at low altitude on oxygen-dependent patients with end-stage lung disease.

OBJECTIVE: To assess the effect of lowering altitude to that of the lowest place on earth (Dead Sea) on arterial oxygenation and exercise performance in patients with hypoxemia and end-stage lung disease. DESIGN: A cohort of 10 patients. SETTING: Pulmonary function laboratories in Jerusalem, Israel, and at the Dead Sea. PATIENTS: 10 patients with end-stage lung disease who were receiving long-term oxygen therapy. The 4 males and 6 females were 12 to 77 years old. Four patients had chronic obstructive pulmonary disease; 2 had cystic fibrosis; 3 had pulmonary fibrosis; and 1 had pulmonary hypertension (thromboembolic). Mean forced vital capacity was 1.54 L (54% of predicted value) and mean forced expiratory volume in 1 second was 0.85 L (35% of predicted value). MEASUREMENTS: Spirometry, blood gas analysis, progressive exercise testing, and sleep oximetry were done in Jerusalem (altitude, 800 m above sea level; barometric pressure, 696 mm Hg); the same measurements were done 6 days after arrival at the Dead Sea (altitude, 402 m below sea level; barometric pressure, 800 mm Hg) and then 7 to 14 days later in Jerusalem. RESULTS: Arterial oxygenation increased from a median partial pressure of arterial oxygen of 51.6 mm Hg in Jerusalem to 67.0 mm Hg at the Dead Sea, an increase of 15.2 mm Hg (95% CI of paired difference, 4.1 to 20.4 mm Hg; P = 0.001). Partial pressure of arterial carbon dioxide increased from a median of 43.2 to 45.9 mm Hg, an increase of 2.7 mm Hg (CI, 0.5 to 6.4 mm Hg; P = 0.004), with a borderline significant change in the alveolar-arterial gradient. Arterial oxygen saturation increased from a median of 87.7% to 92.8%, a change of 4.8% (CI, 1.9% to 9.8%; P = 0.003). Exercise performance also improved as maximum oxygen uptake increased from a median of 827 mL/min to 1056 mL/min, an increase of 203 mL/min (CI, 54 to 388 mL/min; P = 0.006). Sleep oximetry also improved as median arterial oxygen saturation measured during sleep increased from 85% to 90%, a change of 5% (CI, 2% to 7%; P = 0.005), and percentage of sleep time with an oxygen saturation rate of 90% or more increased from a median of 24% to 73%, a change of 49% (CI, 20% to 87%; P = 0.02). No change in spirometry was noted. All patients felt less dyspneic and reported improved functional capacity with reduced need for oxygen. CONCLUSION: Descent to low altitude can improve arterial oxygenation, exercise performance, and sleep oximetry and consequently the quality of life in patients with hypoxemia and advanced lung disease.

Computerized respiratory muscle training in children with Duchenne muscular dystrophy.

The present study describes the use of simple video games for a 5-week regimen of respiratory muscle training in 15 patients with Duchenne muscular dystrophy (DMD) at various stages of the disease. The games were re-arranged to be operated and driven by the respiratory efforts of the patient and to incorporate accurate ventilation and time measurements. Improvement in respiratory performance was determined by maximum voluntary ventilation (MVV), maximal achieved ventilation (VEmax) during a progressive isocapnic hyperventilation manoeuvre (PIHV) and the PIHV duration. The actual training period was 23 +/- 4 days (mean +/- S.D.) at ventilatory effort of 46 +/- 6% MVV, for 10 +/- 3 min day-1. Patients with moderate impairment of lung function tests (LFT) showed an improvement in MVV, VEmax, and duration of PIHV of 12 +/- 7% (p < 0.02), 53 +/- 25% (p < 0.001) 57 +/- 21% (p < 0.01), respectively. Improvements correlated with actual training time and ventilation level, %MVV, but negatively correlated with years of immobilization and with the initial MVV. We conclude that computerized respiratory games may be applied for breathing exercises and may improve respiratory performance in recently immobilized children with DMD who have moderate impairment of LFT.

Comparison of airway resistance and total respiratory system resistance in infants.

Airway resistance (Raw) can be measured throughout the respiratory cycle by whole body plethysmography. Total resistance of the respiratory system (Rrs) can be measured from the relaxed expiration that follows end inspiratory occlusion. The purpose of this study was to compare the two methods in normal infants and in infants with airway obstruction of different types and severity. Fifteen infants with essentially normal lungs aged 24.6 +/- 18.0 (SD) wk, nine infants with congenital stridor aged 36.0 +/- 17.3 wk, and eleven wheezy infants aged 20.1 +/- 11.3 wk had simultaneous measurements of Raw and Rrs. Rrs was similar to Raw both during inspiration and expiration in the normal infants, to all expiratory Raw in those with congenital stridor, and to all inspiratory and early expiratory Raw in the wheezy infants. Raw was markedly and significantly higher than Rrs during mid and late inspiration in infants with congenital stridor and during late expiration in the wheezy infants. We conclude that Rrs is a good estimate of Raw in normal infants and of early expiratory Raw in all infants. In infants with airway obstruction, Rrs does not reveal the dynamic changes in Raw during tidal breathing, nor can it differentiate between infants with upper and lower airway obstruction.

Bronchial provocation determined by breath sounds compared with lung function.

Bronchial provocation testing with methacholine was undertaken in 15 children aged 5 to 8 years with obstructive lung disease, mostly asthma (13/15). The methacholine was inhaled during two minutes of tidal breathing in increasing concentrations. After each inhalation, lung function was measured and clinical signs recorded independently by two observers unaware of each other's results. The logarithm of the concentration of methacholine which caused wheezing over the trachea correlated closely with the logarithm of the concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (FEV1) but was 52% greater on average. At the end of the test there was a mean (SD) fall in FEV1 of 33.3 (7.4)% and a fall in oxygen saturation of 5.2 (3.1)%. Bronchial provocation testing by listening for wheeze over the trachea is a safe technique, which correlates with objective measures of lung function in young children.

Nonspecific bronchial reactivity in asthmatic children depends on severity but not on age.

Bronchial reactivity to inhaled methacholine was measured by the steady-state tidal breathing method in asthmatic children aged 1 to 17 yr. The children were divided into three clinical groups according to their minimal therapeutic requirements: mild asthma, children requiring infrequent treatment with inhaled beta-agonists (81 patients); moderate asthma, children requiring daily preventive treatment with either cromolyn sodium or slow-release theophylline (67 patients); and severe asthma, children requiring daily preventive treatment with oral or inhaled steroids (34 patients). They were also divided into three age groups: from 1 to 6 yr, tested by using bronchial provocation with tracheal auscultation (BPTA) to determine the methacholine concentration causing wheezing (PCW); and from 7 to 11 yr and 12 to 17 yr, using lung function testing to determine the concentration causing a 20% fall in FEV1 (PC20). For the whole group the mean level of bronchial reactivity to methacholine correlated inversely with the severity of bronchial asthma according to the minimal drug requirements (p less than 0.0001) and was similar over the whole age range (p less than 0.9965) for each severity grouping. In the older children the difference between moderate and severe asthma was not significant, but this may have been a result of the effect of corticosteroids in the severe group. We concluded that age has no significant effect on the methacholine response in asthmatic children over a wide age range.

Effect of hyperoxia on bronchial response to inhaled methacholine.

Bronchial reactivity to methacholine (MCH) under normoxic and hyperoxic conditions was studied in a double-blind controlled study in 10 normal subjects and nine asthmatic patients. The normal volunteers were challenged while breathing dry, 21% and 100% O2, and the maximal percent falls in forced expired volume in is (FEV1) following inhalation of the highest concentration of MCH (64 mg/ml) were 8 +/- 5% and 9 +/- 8%, respectively; P = NS. The asthmatic patients had their MCH challenge breathing the same gas composition and the provocative concentrations that caused a 20% fall in FEV1 (PC20) were 0.18 mg/ml (range 0.06-5.73) and 0.25 mg/ml (range 0.07-8.49), respectively, which were statistically not significantly different. We conclude that in humans, 100% O2 does not affect bronchial reactivity to MCH.

Corticosteroids do not affect the clinical or physiological status of infants with bronchiolitis.

The treatment of infants aged 1.5-11.0 months suffering from acute bronchiolitis with a combination of inhaled albuterol and systemic corticosteroids or inhaled albuterol and placebo was compared in 50 infants in a double blind study. The mean initial clinical score and the rate of improvement was similar in the two groups. The mean +/- SD hospital stay was 5.0 +/- 1.2 days for the steroid group and 5.2 +/- 1.7 days for the placebo group. Lung function was measured in 14 infants (7 from each group) and showed evidence of increased lung volumes and severe airway obstruction in the acute stage (the mean values for the steroid group were: TGV, 31 mL/kg; SGaw, 0.104 L/s.cmH2O; VmaxFRC, 12.9 mL/s/kg; for the placebo group: TGV, 35 mL/kg; SGaw, 0.104 L/s.cmH2O; VmaxFRC, 8.5 mL/s/kg) which had improved 2-4 weeks later (steroid group: TGV, 25 mL/kg; SGaw, 0.168 L/s.cmH2O; VmaxFRC, 21.6 mL/s/kg; -placebo group: TGV, 24 mL/kg, SGaw, 0.198 L/s.cmH2O, VmaxFRC, 17.5 mL/s/kg). There were no significant differences of thoracic gas volume, specific airway conductance, and forced expiratory flow at resting lung volume between the two groups, either in the acute or convalescent stages. We conclude that corticosteroids do not change the rate of clinical improvement in acute bronchiolitis, nor do they effect lung function 2-4 weeks later.