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.     

Effect of nebulized salbutamol in preterm infants during the first year of life.

The acute effect on lung function of nebulized salbutamol and saline (placebo) has been investigated in preterm infants at follow-up. Twenty two premature infants, median gestational age 29 weeks (range 26-32 weeks) and birthweight 1,264 g (720-1,800 g), were studied at a median postnatal age of 7 months (range 6-9 months). Nine of the infants had recurrent respiratory symptoms; they coughed and/or wheezed at least 3 days per week for the previous 4 weeks. The remaining 13 infants were free from recurrent or persistent respiratory symptoms. Thoracic gas volume (TGV) and airways resistance (Raw) were measured and specific airway conductance sGaw calculated before and 10 min after salbutamol and normal saline given via a nebulizer. Amongst the symptomatic infants administration of nebulized salbutamol was associated with a median reduction in Raw of 25% (p less than 0.01) and also a significant improvement in sGaw (p less than 0.01). In the asymptomatic infants neither Raw nor sGaw changed significantly. Nebulized saline caused no significant change in lung mechanics in either the symptomatic or asymptomatic infants. We conclude that nebulized salbutamol is an effective bronchodilator for symptomatic preterm infants less than one year of age.     

Randomized, placebo-controlled trial of albuterol and epinephrine at equipotent beta-2 agonist doses in acute bronchiolitis

Our objective was to determine if nebulized racemic epinephrine is more efficacious than nebulized albuterol or saline placebo in the treatment of bronchiolitis in the outpatient setting when dosing is equivalent in terms of beta-2 agonist potency. Sixty-five patients between ages 6 weeks and 24 months with a diagnosis of bronchiolitis, defined as first-time wheezing, upper respiratory symptoms and/or fever, and a Respiratory Distress Assessment Instrument score of at least 4, were randomized to receive 5 mg nebulized albuterol, 5 mg nebulized racemic epinephrine, or an equivalent volume of placebo at 0, 30, and 60 min. The primary outcome measure was need for hospital admission or home oxygen. Secondary outcome measures were changes in clinical scores and oxygen saturations. There were no significant statistical differences between groups in terms of need for hospital admission or outpatient management with home oxygen therapy. There were no differences between groups in terms of changes in clinical scores or oxygen saturations. Racemic epinephrine and albuterol at equivalent doses had no effect on the need for hospitalization or supplemental oxygen in bronchiolitis in the outpatient setting compared to nebulized saline placebo, though this study may have missed less dramatic clinical effects due to small sample size.     

Infants with upper respiratory illnesses have significant reductions in maximal expiratory flow

We studied maximal expiratory flows at functional residual capacity (VmaxFRC) obtained by use of the chest compression technique in 9 infants who had signs of upper respiratory illness (URI) at the time of testing, and in 9 infants who were symptom-free but whose parents reported they had a URI in the previous month. When compared to 109 infants with no URI, infants with current URI had 40% lower VmaxFRC (mean +/- SD: 125.7 +/- 54.5 mL/s vs. 73.6 +/- 53.6 mL/s; P less than 0.01). Infants with a past URI had mean values for VmaxFRC (120.2 +/- 50.2 mL/s) that were not significantly different from those of infants with no URI. Changes in the shape of the flow-volume loop analogous to those reported in infants with lower airway obstruction were also noticed in infants with current URI. These findings suggest that, as in older children and adults, clinically unapparent alterations in lower airway function occur during URI in infants.     

Immediate effect of various treatments on lung function in infants with cystic fibrosis

The immediate effect of four different modes of treatment was assessed by lung function tests on 19 infants with cystic fibrosis (CF) during the first year of life. The regimens were applied in a randomized fashion and consisted of aerosol inhalation of salbutamol (n = 8; SAL), aerosol inhalation of N-acetyl cysteine (n = 5; AC), chest physiotherapy (n = 6; CPT), and combined treatment with aerosol inhalation of SAL and AC followed by CPT (n = 6; COMB). Pulmonary function was measured before and shortly after therapy with each mode of treatment. Thoracic gas volume (Vtg) and specific airway conductance (SGaw) were measured by an infant whole body plethysmograph, and forced expiratory flow at resting lung volume (VmaxFRC) was determined with a thoraco-abdominal squeeze jacket. There was no correlation between baseline lung function and changes in any parameter due to treatment. Overall group comparison showed that the combined therapy resulted in a significant improvement in lung function when compared to any of the three treatments applied separately. There was no significant change in lung volumes in any individual group, but SGaw and VmaxFRC showed a small but significant improvement following the COMB treatment when compared with AC or CPT.     

Gastroesophageal reflux in infants with wheezing.

The relation between silent gastroesophageal reflux (GER) and respiratory problems such as persistent wheezing in infants is not well-established. Between January 1994 and June 1997, we evaluated the incidence of GER in 84 otherwise healthy infants referred to the Pediatric Pulmonary Medicine Division at Kosair Children's Hospital for evaluation of daily wheezing, and we followed their clinical course for 18 months. All underwent 24-hr esophageal pH studies to evaluate GER. The pH probe study was performed at a mean age of 8.74 +/- 4.6 months. Infants with a positive GER study were treated with an H2 receptor antagonist (H2RA) and a prokinetic agent for a mean of 5.6 +/- 2.4 months. At first follow-up visit 3 weeks after esophageal pH studies infants treated with an H2RA and those who did not have GER but continued with daily wheezing were started on flunisolide nasal solution (0.025%) delivered by nebulizer (125 mcg t.i.d.). Infants in both groups were followed every 1-2 months for a mean of 18 months and if clinically improved, attempts to decrease their daily asthma medications were made. Fifty-four of 84 (64%) had positive esophageal pH studies (GER-positive group), and 24 of them (44%) had no gastrointestinal symptoms suggestive of GER. Thirty patients had normal esophageal pH studies (GER-negative group). Twenty-two of these 30 (73%) infants without GER required nebulized flunisolide, compared to 13 of 54 (24%) infants with GER (P < 0.0005). Thirty-five of 54 (64.8%) infants with GER were able to discontinue all daily asthma medications within 3 months of starting antireflux therapy, while none of the infants without GER were able to discontinue daily asthma medications during the follow-up period (P < 0.0005). We conclude that silent GER is common in infants with daily wheezing, and controlling GER improves morbidity and decreases the need for daily asthma medications.     

Lung function in infancy and childhood following neonatal intensive care

Pulmonary function studies were performed in 11 neonatal intensive care survivors both during infancy and later in childhood. Lung function was compared with the respiratory support given in the neonatal period. The mean +/- SE thoracic gas volume was 96 +/- 4% predicted in infancy and rose to 122 +/- 8% predicted during childhood (P less than 0.005). The specific airway conductance (SGaw) in infancy was 57 +/- 7% predicted and rose to 90 +/- 8% predicted in childhood (P less than 0.0025). Abnormalities in SGaw were found only in ventilated infants, and there was a negative logarithmic correlation between the treatment score in the neonatal period and the SGaw in both infancy and childhood. The data indicate a long-term improvement in airway conductance of moderately affected infants with the development of mild hyperinflation in childhood possibly resulting from residual small airway abnormalities despite a symptomless clinical course. The residual abnormalities in prematurely born infants were in proportion to the intensity of treatment required in the neonatal period.     

Airway responsiveness to cold, dry air in normal infants

Reactive airway disease may be related to genetic, infectious, and environmental factors. The latter two have been well documented, but there are no data on nonspecific airway responsiveness in normal infants prior to any insult to the respiratory tract. We measured forced expiratory flow by the thoracic compression technique and lung volume in 30 normal infants before and after challenge with cold, dry air (CDA) and compared the results with those in 12 infants who did not receive CDA challenge. As a group, infants challenged with CDA had a mean decrease in VmaxFRC of 17.9 +/- 24.1% SD. This was significantly different (P less than 0.01) from the lack of change (+ 1.3 +/- 18.1% SD) seen in the control group. We conclude that nonspecific airway reactivity may exist from early infancy and may predate any known lung injury. The relationship of this airway responsiveness to subsequent reactive airway disease and other respiratory illnesses is unknown and requires longitudinal study.     

Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial.

Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract infection in infancy. To date, there is no effective therapy for RSV bronchiolitis. In order to investigate the efficacy of clarithromycin in the treatment of RSV bronchiolitis, the present authors conducted a randomised, double-blind, placebo-controlled trial comparing clarithromycin with placebo in 21 infants with a diagnosis of RSV bronchiolitis. The infants were randomised to receive clarithromycin or placebo daily for 3 weeks. Levels of interleukin (IL)-4, IL-8, eotaxin, and interferon-gamma were determined in plasma, before and after treatment, using ELISA. Six months after treatment, parents were surveyed as to whether their child had experienced wheezing within the previous 6 months. Treatment with clarithromycin was associated with a statistically significant reduction in the length of hospital stay, the duration of need for supplemental oxygen and the need for beta(2)-agonist treatment. There were significant decreases in plasma IL-4, IL-8 and eotaxin levels after 3 weeks of treatment with clarithromycin. Readmission to the hospital within 6 months after discharge was significantly lower in the clarithromycin group. In conclusion, clarithromycin has statistically significant effects on the clinical and laboratory findings in respiratory syncytial virus bronchiolitis. Therefore, clarithromycin treatment may be helpful in reducing the short-term effects of respiratory syncytial virus bronchiolitis.     

Eosinophil cationic protein in infants with respiratory syncytial virus bronchiolitis: predictive value for subsequent development of persistent wheezing

Infants with acute bronchiolitis during the first months of life are at increased risk of developing persistent wheezing and bronchial asthma later in life. The study of eosinophil cationic protein (ECP) suggests that eosinophil-related inflammatory mechanisms may play a role in respiratory syncytial virus (RSV) bronchiolitis. The aim of our study was to verify whether serum ECP (s-ECP) measurements are useful in predicting the development of persistent wheezing in children affected by RSV bronchiolitis during a 5 years follow-up period. Forty-eight infants were enrolled prospectively (mean age: 153.5 days). All had a clinical and radiological diagnosis of acute bronchiolitis and confirmed RSV infection. Peripheral eosinophil counts, levels of s-ECP, and serum IgE concentrations were measured during bronchiolitis. Five years later the children were re-evaluated in regard to their respiratory symptoms (standardized questionnaires) and atopic status (specific IgE levels). We observed significantly higher s-ECP levels (P < 0.001) at enrollment in subjects who developed persistent wheezing compared to subjects who did not show late wheezing. Initial s-ECP values allowed significant and correct prediction of persistent wheezing (P < 0.001). The risk to develop respiratory symptoms was 9.73 higher for infants with s-ECP levels > or = 8 microg/L than for those with s-ECP levels <8 microg/L (P < 0.0001). In conclusion, our study suggests that s-ECP levels in infants with bronchiolitis are useful in predicting the risk to develop wheezing in the subsequent 5 years.     

Efficacy of nebulized epinephrine versus salbutamol in hospitalized infants with bronchiolitis

We enrolled 30 infants (median age 3 months, range 1-12 months), hospitalized for bronchiolitis in a randomized double-blind trial, to examine the efficacy and safety of nebulized epinephrine compared to salbutamol. Once admitted, patients were treated with either nebulized 0.5 mg of an 0.1% epinephrine solution (0.5 mL in 3.5 mL normal saline (NS)) or 2.5 mg nebulized salbutamol (0.5 mL in 3.5 mL NS). They were evaluated daily before and after nebulization until discharge. The outcome measures used were: baseline clinical score (based on respiratory rate, subcostal retraction, presence of wheezing, and O2 requirement), change in clinical O2 score after nebulization, duration of O2 therapy, and duration of hospitalization. A significant improvement in the clinical score was noted on the first day of hospitalization in subjects receiving epinephrine (P = 0.025); that change was not seen in those on salbutamol (P = 0.6). Nebulized epinephrine decreased the baseline clinical score faster than salbutamol (P = 0.02), though on the fourth study day there was no significant difference between the two scores. On the fourth and fifth days of study there were more patients hospitalized in the salbutamol group than in the epinephrine group (P = 0.03 vs. P = 0.025). No adverse effects were associated with nebulized therapy. We conclude that nebulized epinephrine is a more effective agent than salbutamol in the initial treatment of bronchiolitis and is equally safe.     

Bronchial reactivity in infants in acute respiratory failure with viral bronchiolitis

Airway reactivity and the effects of bronchodilators in infants are controversial. We studied the response to bronchodilator treatment in 14 mechanically ventilated infants (mean age, 2.74 months; range, 0.6-5.9) in respiratory failure caused by respiratory syncytial virus (RSV)-associated bronchiolitis. Sixteen infants without lung disease, undergoing elective surgery, provided normal values. Maximum expiratory deflation flow-volume (DFV) curves were produced by manual inflation of the lungs with an anesthesia bag to a predetermined static airway pressure followed by rapid deflation with a negative airway pressure before and after administration of bronchodilator. At baseline, the bronchiolitis group had a forced vital capacity (FVC) of 34.5 +/- 3.6 ml/kg compared with 41.8 +/- 1.5 ml/kg in the normal group; maximum expiratory flow rate at 25% of FVC (MEF25) was 10.2 +/- 2.0 ml/kg/s compared with 27.3 +/- 2.0 ml/kg/s in the normal group. The clinical and radiologic impression was severe lower airway obstruction and air trapping. After administration of bronchodilator, FVC did not increase significantly, but MEF25isov increased by over 30% in 13 of 14 infants. Mean MEF25 increased by 148 +/- 43.2% to 21.7 +/- 3.9 ml/kg/s (P less than 0.02). These findings indicate that during the acute phase of severe RSV-positive bronchiolitis most infants have airway reactivity that responds positively to bronchodilator treatment.     

Paradoxical response to nebulized ipratropium bromide in pre-term infants asymptomatic at follow-up.

Lung function measurements were performed before and after bronchodilator, nebulized ipratropium bromide (10 micrograms kg-1), in 20 pre-term infants [median gestational age 28 weeks (range 23-32 weeks) at a median postnatal age of 10 months (range 6-16 months)]. Eight of the infants had recurrent respiratory symptoms. Thoracic gas volume (TGV) and airways resistance (Raw) were measured by a plethysmographic technique and functional residual capacity (FRC) by a helium gas dilution technique. There was no significant change in either TGV or FRC following bronchodilator in the symptomatic and asymptomatic infants. Nebulized bronchodilator resulted in a significant improvement in Raw amongst the symptomatic infants (P less than 0.05), but a paradoxical response, that is, a deterioration (P less than 0.05) in Raw amongst the asymptomatic infants. In three asymptomatic infants, lung function measurements were repeated before and after nebulized saline and a similar deterioration in Raw was noted. We conclude the demonstration of respiratory symptoms at follow-up is useful in predicting infants who would have a beneficial response to nebulized ipratropium bromide.     

Aerosolized budesonide in asthmatic infants: a double blind study

The efficacy of nebulized budesonide (0.5 mg b.i.d.) against placebo was evaluated in the management of asthma in 23 infants, aged 3 to 17 months, using a double blind crossover design. After an initial treatment period of 2 weeks placebo and budesonide were randomly administered during two consecutive treatment periods of 1 month. The progress of the patients was monitored using diary score cards, the number of salbutamol doses needed during the treatment periods, clinical examinations using standardized scoring cards, and registration of parents' preference period. Although there was a tendency toward fewer wheezing periods during budesonide, the results of the diary score cards were not significantly different between the budesonide period and the placebo period. The number of salbutamol doses used was also the same during both periods. Clinical examination after budesonide revealed less rhinitis and a less pathological lung auscultation, but the difference between the two periods was also not significant. Furthermore, the parents' preference could not distinguish between budesonide and placebo. We conclude that the trends in favor of nebulized budesonide are not significant and do not suggest that the suspension is effective in severe infantile asthma.     

Inhaled nebulized adrenaline improves lung function in infants with acute bronchiolitis

Beta2-agonists have questionable symptomatic effect in infants with acute bronchiolitis, whereas inhaled, nebulized racemic adrenaline, commonly used in Norway, appears (clinically) to be effective. Limited lung function observations during acute bronchiolitis exists, and less for assessing possible effects inhaled adrenaline. In this preliminary study, tidal flow-volume loops were measured in 16 infants with acute bronchiolitis and seven healthy controls (mean age 7.9 and 4.4 months, respectively), with repeated measurements 15 min after inhaled nebulized racemic adrenaline (4 mg diluted in 2 ml saline) in nine bronchiolitis patients. The ratio of time to reach peak tidal expiratory flow to total expiratory time (tPTEF/tE) was significantly reduced in children with acute bronchiolitis (mean, 95% CI) (0.08, 0.05-0.10) compared to controls (0.31, 0.18-0.43), with significant improvement after inhaled racemic adrenaline 0.19 (0.13-0.25), parallel with significant clinical improvement. Lung function (tPTEF/tE) was reduced in infants with acute bronchiolitis and improved significantly after inhaled racemic adrenaline. Inhaled racemic adrenaline is potentially an important alternative for treating infants with acute bronchiolitis.     

Oral steroid-sparing effect of two doses of nebulized fluticasone propionate and placebo in patients with severe chronic asthma

Inhaled steroids, delivered by metered dose aerosol and dry powder inhalers, have proved effective in reducing the need for oral steroids in patients with oral steroid-dependant asthma. This randomized, double-blind study, compared the efficacy and tolerability of nebulized fluticasone propionate (FP Nebules), 2 mg b.d. (FP 4 mg) and 0.5 mg b.d. (FP 1 mg) with placebo, on the reduction of oral steroid requirement in 301 adult patients with oral steroid-dependent asthma. Primary efficacy was assessed by the reduction in daily oral steroid dose. Secondary efficacy parameters included daily diary card peak expiratory flow (PEF), day and night-time symptoms and clinic lung function measurements. Safety was assessed by adverse event monitoring and serum cortisol levels. After 12 weeks of treatment the adjusted mean +/- SEM reduction in oral prednisolone was significantly greater in the FP 4 mg group (4.44 +/- 0.98 mg day-1) compared with FP 1 mg (2.16 +/- 1.00 mg day-1, P = 0.039) and placebo (1.20 +/- 1.02 mg day-1, P = 0.004). A higher percentage of patients discontinued the use of oral steroids with FP 4 mg (37%) compared with FP 1 mg (26%, P = 0.038) and placebo (18%, P < 0.001). Following treatment, the adjusted mean morning PEF showed a trend in favour of FP 4 mg (280 +/- 41 min-1) compared with placebo (270 +/- 51 min-1, P = 0.053) and the evening PEF was significantly higher with FP 4 mg (305 +/- 41 min-1) compared with FP 1 mg (292 +/- 41 min-1, P = 0.010). FP 4 mg resulted in a significantly higher percentage of days when the patients were free from daytime (P = 0.036) and night-time (P = 0.021) wheeze, compared with placebo. Significantly fewer patients withdrew from the FP 4 mg group compared with the other two groups (vs. FP 1 mg, P = 0.003; vs. placebo, P = 0.032). All three treatments were well tolerated and the incidence of adverse events was similar between the groups. FP Nebules at a daily dose of between 1 and 4 mg are a safe and effective means of reducing the oral steroid requirement of patients with chronic oral steroid dependent asthma.     

High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients

One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.     

Airway responsiveness in infants following bronchiolitis.

Airway responsiveness to inhaled methacholine was assessed in 18 infants, 4 and 10 months old, following bronchiolitis. Pulmonary function was measured from partial expiratory flow-volume curves generated by the rapid compression technique. Sleeping infants inhaled increasing concentrations of methacholine until maximal expiratory flows at functional residual capacity (VmaxFRC) decreased by 30% or 2.5 mg/mL was inhaled. Airway responsiveness was quantitated by: 1) the threshold concentration (log TC) required to decrease VmaxFRC by 2 standard deviations from baseline; 2) the concentration required to decrease VmaxFRC by 30% (log PC30); and 3) the slope of the dose-response curve between TC and PC30 (log SPC30). At both the first and second evaluation, the bronchiolitic infants had lower baseline VmaxFRC (% pred.) than 24 control infants. In addition, the bronchiolitic infants had heightened airway responsiveness compared to controls, demonstrating lower values for logTC and logPC30 and steeper slopes to their dose-response curves (logSPC30). After accounting for the relationship between airway responsiveness and age, the occurrence of bronchiolitis was found to be a significant independent factor 10 months but not 4 months following bronchiolitis. The bronchiolitic infants did not demonstrate the decline in airway responsiveness with increasing age that occurs in normal infants. We conclude that infants exhibit heightened airway responsiveness following bronchiolitis.     

Nebulized flunisolide in infants and young children with asthma: A pilot study

The role of nebulized flunisolide solution in controlling recurrent respiratory symptoms was assessed in a double-blind placebo-controlled parallel study on 23 infants and small children (mean age, 14 2 months) with bronchial asthma. Five of the 12 children in the placebo group and 1 of the 11 patients on active treatment had to be withdrawn from the study. Flunisolide significantly improved symptom scores of wheezing and cough. The rescue treatments with salbutamol did not differ between the two groups during the study. Parents considered the active treatment effective in all the patients, while the placebo was considered useful in 4 of 7 children. No side effects were detected with either treatments. This study indicates that nebulized flunisolide may be an effective treatment for infants with recurrent wheezing and cough. Pediatr Pulmonol. 1996; 21:310–315. © 1996 Wiley-Liss, Inc.     

Bronchial responsiveness and lung function in recurrently wheezy infants

Although most wheezy infants are considered asthmatic, they generally respond poorly to antiasthma treatment, and there is inadequate knowledge about the pathologic mechanisms that cause wheezing at this age. The aim of this study was to determine whether the strong association between wheezing and bronchial responsiveness (BR) seen in older subjects was also present in infants. We compared BR with inhaled histamine in 19 recurrently wheezy infants with a group of age-, height-, weight-, and sex-matched control infants. Maximal flow at FRC (VmaxFRC) was determined from partial expiratory flow-volume curves generated using the "squeeze" technique. Histamine was delivered during 1 min of tidal breathing in doubling concentrations from 0.125 g/L to a maximum of 8 g/L or until VmaxFRC fell by 40% (PC40). The median baseline VmaxFRC for the wheezy infants was 100.0 ml/s compared with 182.0 ml/s for the control infants (p less than 0.01). However, there was no significant difference in the PC40 between the two groups (2.1 versus 2.3 g/L).