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PubMed2002

Infants with flow limitation at 4 weeks: outcome at 6 and 11 years.

Within a longitudinal study of lung function in 243 infants, we identified a group of 23 individuals with flow limitation in tidal expiration. In infancy, flow-limited children have reduced lung function and increased airway responsiveness (AR), and at 2 years of age they are diagnosed with asthma more frequently. We hypothesized that these observations would persist throughout childhood. Data from ages 3 to 11 years were analyzed. Only at 4 years of age did the flow-limited group have increased wheeze compared with other cohort members (odds ratio, 4.25; 95% confidence interval [CI], 1.11 to 16.2; p = 0.04; n = 114). At 6 years of age, 117 cohort members were seen. The flow-limited group (n = 14) had greater AR (p = 0.009) and reduced mean FEV(1) (131 ml; 95% CI, 16 to 246; p = 0.03) and FEF(25-75) (0.28 L/second; 95% CI, 0.05 to 0.52; p = 0.02). At 11 years of age, 183 children were seen and the flow-limited group (n = 18) had greater AR (p = 0.02) and a trend toward reduced mean FEF(25-75) (0.24 L/second; 95% CI, -0.02 to 0.49; p = 0.08). Atopy and parental asthma were not increased in the flow-limited group. We suggest that the physiologic abnormality that causes flow limitation in early infancy may identify an at-risk group, different from asthma, who have reduced lung function and increased airway responsiveness in later life.

Child↗
PubMed2002

Spirometry in 3- to 6-year-old children with cystic fibrosis.

Spirometry is routinely used to assess pulmonary function of older children and adults with cystic fibrosis (CF); however, few data exist concerning the preschool age group. We have reported normative spirometric data for 3- to 6-year-old children. The current study was designed to assess a similarly aged group of clinically stable patients with CF. Thirty-three of 38 children with CF were able to perform 2 or 3 technically acceptable maneuvers. These patients had significantly decreased FVC, FEV(1), FEV(1)/FVC, and FEF(25-75) when expressed as z scores (number of SD from predicted): -0.75 +/- 1.63, -1.23 +/- 1.97, -0.87 +/- 1.33, and -0.74 +/- 1.63, respectively. There were significant positive correlations of the Brasfield radiological score with FVC and FEV(1) z scores (r(2) = 0.26, p < 0.01 and r(2) = 0.24, p < 0.01). In addition, homozygous patients for the DeltaF508 mutation had lower z scores for FVC (-1.21 versus 0.47, p < 0.01) and FEV(1) (-1.38 versus 0.21, p < 0.05) than heterozygous patients. Of the 14 patients who had full flow-volume spirometric measurements during infancy, 10 had FEF(25-75) z scores greater than -2 at both evaluations. Our findings suggest that spirometry can successfully be used to assess lung function in preschool children with CF and has the potential for longitudinal assessment from infancy through adulthood.

Age Factors↗
PubMed2005

High-resolution computed tomography imaging of airway disease in infants with cystic fibrosis.

RATIONALE: The development of early lung disease in patients with cystic fibrosis (CF) remains poorly defined. OBJECTIVE: Determine whether asymptomatic infants with CF have evidence for changes in airway structure when assessed by high-resolution computed tomography, and whether airway structure correlates with airway function in this age group. METHODS: Thirteen infants with CF (8-33 mo) and 13 control infants (7-25 mo) were evaluated. Airway wall and lumen areas were measured from three 1-mm-thick cross-sectional images obtained from upper, middle, and lower lobes during a respiratory pause with the lungs inflated to an airway pressure of 20 cm H2O. Lung tissue density was measured from images obtained during a respiratory pause at FRC. Forced expiratory flows were measured by the rapid thoracic compression technique in 11 infants with CF. RESULTS: Airway wall area increased more per unit increase in airway size, whereas airway lumen area increased less per unit increase in airway size in the CF than in the control group. Among infants with CF, a greater ratio of wall to lumen area correlated with lower airway function. In addition, lung density at relaxed (passive) FRC was lower for infants with CF than for control infants (0.38 vs. 0.43 g/ml; p < 0.02). CONCLUSIONS: Our results indicate that infants with CF have thickened airway walls, narrowed airway lumens, and air trapping, when assessed by high-resolution computed tomography, and measurements of airway structure correlated with airway function.

Case-Control Studies↗
PubMed2002

Relative ability of full and partial forced expiratory maneuvers to identify diminished airway function in infants with cystic fibrosis.

The tidal and raised volume rapid thoracoabdominal compression techniques are increasingly used to detect diminished airway function in infancy. The aim of this study was to assess the relative ability of parameters measured by these techniques to identify diminished airway function in infants newly diagnosed with cystic fibrosis (CF) with and without clinical evidence of prior lower respiratory illness. A cross-sectional, prospective study design was used in which maximal flow at functional residual capacity (VmaxFRC) from the tidal technique and FVC, FEV0.5, FEF75, and FEF25-75 from the raised volume technique were measured in 47 infants with CF and 187 healthy infants of similar body size, sex distribution, ethnic group, and exposure to maternal smoking. Multiple linear regression was used to assess group differences and to calculate SD scores for each parameter for the infants with CF. Airway function was also compared with clinical assessments of respiratory status made by pediatric pulmonologists. FEV0.5 was significantly diminished in 13 infants with CF, of whom 4 had been identified by clinicians as having normal respiratory status. Only one infant with CF had a VmaxFRC below the estimated normal range. Airway function is diminished in infants with CF irrespective of prior lower respiratory illness and in those whose respiratory status is considered normal by pediatric pulmonologists. In infants with CF, the raised volume technique identified diminished airway function more frequently than the tidal technique.

Age Factors↗
PubMedDate not supplied

Can a low or moderate dose of inhaled budesonide replace oral non-steroidal anti-asthma treatment?

The efficacy of inhaled budesonide was assessed as an adjunct to and as a replacement for oral bronchodilators in an open study of 27 asthmatic patients. The patients had been treated regularly with oral bronchodilators but not with oral inhaled, or nasal steroids during the 2 3 months prior to the study. The study consisted of four treatment periods: 1, oral bronchodilator plus inhaled placebo for 1 week; 2, oral bronchodilator plus 400 micrograms inhaled budesonide twice daily for 3 weeks; 3,400 micrograms inhaled budesonide twice daily for 3 weeks; 4,200 micrograms inhaled budesonide twice daily for 3 weeks. Lung function measurements increased when budesonide was included with oral bronchodilators and there was a corresponding decrease in symptoms and rescue inhaler usage. Removal of oral bronchodilators from therapy did not significantly alter lung function and symptoms, whereas decreasing the dose of budesonide produced a slight reduction in peak expiratory flow and an increase in inhaled bronchodilator consumption.

Administration, Inhalation↗
PubMed2002

Time domain and flow indices of bronchial hyperresponsiveness: association with asthma symptoms, atopy and smoking.

Conventional measures of bronchial hyperresponsiveness (BHR) are only weakly associated with respiratory symptoms in epidemiological studies. Partial and maximal forced expiratory manoeuvres were recorded during histamine challenge testing in 1,959 young male farmers. Analysis was performed to test whether novel measures of BHR, using alternative flow and time domain indices, are more closely associated with asthma symptoms, smoking status and atopy than forced expiratory volume in one second (FEV1) and conventional measures of BHR. The first moments to 75% and 90% of the forced vital capacity (FVC) were calculated from full (F) and partial (P) forced expiratory manoeuvres (i.e. alpha1 75%F, alpha1 75%P), together with the instantaneous flows when 40% and 30% of the FVC remained to be expired (MEF40 and MEF30). BHR was measured by the provocative dose causing a 20% change (PD20) in the FEV1 and alpha1 75%, and also by the method of log dose slopes (LDS). Asthma was diagnosed from symptoms associated with asthma in 158 (8.1%) of the subjects. PD20 FEV1 could only be recorded in 190 subjects (9.7%), of whom only 48 had asthma, whereas LDSFEV1 was recorded in 1,725 (88%) subjects. From the prechallenge data, alpha1 75%, expressed as standardised residuals, showed the largest difference between smokers with and without asthma symptoms, and no indices showed significant differences between nonsmokers with and without asthma symptoms. From BHR data in both smokers and nonsmokers, LDSFEV1 showed one of the largest differences between those with and without asthma symptoms. With smoking status and atopy accounted for, the greatest partial correlation with asthma diagnosis was found for LDSMEF40P, and then for LDSFEV1, but LDSMEF40P was measurable in only just over one-half of the subjects. The authors conclude that time-domain indices are promising measures for longitudinal epidemiological studies concerning the relationship between bronchial hyperresonsiveness and environmental exposures. However, indices from the partial flow-volume loop suffer from censored data.

Adult↗
PubMed2006

Does expiratory flow limitation predict chronic dyspnoea in adults with cystic fibrosis?

Tidal expiratory flow limitation (EFL) may promote dynamic hyperinflation and contribute to chronic dyspnoea. The purpose of this study was to assess the contribution of EFL to chronic dyspnoea in adults with cystic fibrosis (CF). The presence of EFL was determined in 102 adults with stable CF (forced expiratory volume in one second (FEV1) 17.3-91.5% predicted) and 20 age-matched control subjects using the negative expiratory pressure technique. Measurements of inspiratory capacity (IC) and spirometry were performed, and chronic dyspnoea was evaluated using the modified Medical Research Council scale. EFL was present in 34 subjects (33%), with 18 subjects flow limited in the sitting position and 16 subjects flow limited only in the supine position. Flow limitation in the sitting position was associated with older age and lower FEV1 compared with flow-limited supine position and non-flow-limited subjects. A significant reduction in IC accompanied EFL in both the sitting and supine positions. Flow limitation in the sitting position was associated with significantly higher levels of chronic dyspnoea. Ordinal regression analysis indicated that EFL was the best predictor of chronic dyspnoea in a model that included FEV1 % pred. Expiratory flow limitation in cystic fibrosis is associated with reduced forced expiratory volume in one second, older age and dynamic hyperinflation. Expiratory flow limitation significantly contributes to chronic dyspnoea in cystic fibrosis.

Adult↗
PubMed1994

Detection of early lung impairment with aerosol bolus dispersion.

The broadening of inhaled aerosol boluses (aerosol bolus dispersion) during respiration provides a noninvasive measure of convective gas mixing in the lungs. In this study, the sensitivity and specificity of this technique for the diagnosis of early lung impairment due to cigarette smoking was evaluated. Two hundred and sixteen randomly selected subjects (126 smokers and 90 nonsmokers) were investigated with aerosol dispersion in comparison to conventional lung function tests. The cumulative cigarette consumption of the subjects was quantified by "pack-years" (PY). Smokers were classified into the following groups: 0 < PY < or = 10; 10 < PY < or = 20; 20 < PY < or = 30; and PY > 30. Forced expiratory volume in one second (FEV1), maximal expiratory flow at 25, 50 and 75% vital capacity (MEF25, MEF50 and MEF75) decreased significantly with increasing cigarette consumption. In comparison to nonsmokers, FEV1 was significantly reduced in smokers of 10 < PY < or = 30, and MEF75 was significantly reduced in smokers of PY > 20. Aerosol bolus dispersion increased with increasing PY. For all groups of smokers, even those with PY < 10, bolus dispersion was significantly increased in comparison to lifelong nonsmokers, indicating alterations in convective gas mixing in the lungs. Calculation of receiver operating characteristics for the lung function parameters under consideration showed that bolus dispersion has a higher sensitivity and specificity than conventional lung function parameters. Hence, the aerosol bolus dispersion test could be a promising epidemiological tool to study early abnormalities in intrapulmonary gas mixing due to environmental factors.

Adult↗
PubMed1997

Atopy, lung function and bronchial responsiveness in symptom-free paediatric asthma patients.

In adolescence, some paediatric asthma patients will become symptom-free and require no further treatment. There is little information on the atopic status, lung function and bronchial responsiveness of these patients. Symptom-free asthma patients (n=118) aged 7.7-19.2 yrs, were evaluated 1 year after termination of therapy. Bronchial asthma had previously been diagnosed on the basis of recurrent wheezing episodes. Atopic status was assessed by skin-prick testing. Baseline lung function was measured by spirometry, flow-volume curve and plethysmography. Bronchial responsiveness was assessed nonpharmacologically by cold dry air challenge. Eighty one patients had at least one positive skin test result, and the remaining 37 were defined as nonatopic. In atopic subjects, the prevalence of bronchial hyperresponsiveness was significantly higher than in nonatopic patients (41 out of 81 versus 7 out of 37; p=0.001). Atopic subjects showed a significantly lower maximal expiratory flow at 25% remaining vital capacity (p<0.05) and a higher residual volume (p<0.05) than nonatopic subjects. Nonatopic subjects were significantly younger than atopic patients (p<0.01). These symptom- and medication-free paediatric and adolescent asthma patients could, thus, be divided into two groups: 1) atopic subjects with a tendency towards bronchial hyperresponsiveness; and 2) nonatopic subjects with better lung function and normal bronchial responsiveness In view of the increased understanding of the epidemiology of early childhood wheezing, these findings support the concept of different pathogenic mechanisms underlying wheezing episodes in early childhood.

Adolescent↗
PubMed1991

Inhaled verapamil-induced bronchoconstriction in mild asthma.

Methacholine challenges were performed in ten subjects with mild asthma at 2 h before and 20 min after placebo or 5, 10, 20, 40, 80, and 160 mg of inhaled verapamil given in a single-blind randomized crossover manner on different days. While verapamil did not have a bronchodilator effect, the 10-mg dose modestly increased the concentration of methacholine required to decrease FEV1 by 20 percent (PC20). The mean (+/- SEM) increase in PC20 from baseline was 2.1 +/- 0.2 times baseline after 10 mg of verapamil, compared to 1.1 +/- 0.1 times baseline after placebo (p less than 0.001). Unexpectedly, bronchoconstriction (greater than 10 percent decrease in FEV1) associated with cough or wheezing was observed in seven of ten subjects at doses of 20 mg or more. This adverse effect was not related to the osmolarity of the nebulized solutions. Thirty minutes before a standardized exercise challenge, 13 subjects inhaled placebo, 10 mg, or the highest dose of verapamil tolerated during the methacholine study (20 to 160 mg) in a double-blind randomized crossover manner. The exercise challenge was aborted in three subjects because of bronchospasm that occurred after administration of the higher dose. The mean (+/- SEM) maximum change in FEV1 after exercise in the ten subjects completing all three regimens of treatment was -17.1 +/- 4.0 percent after placebo, -12.7 +/- 4.3 percent after 10 mg (p less than 0.05), and -6.4 +/- 3.6 percent after the highest dose (p less than 0.05). We conclude that increasing the dose of verapamil above 10 mg did not provide greater benefit but, paradoxically, induced bronchoconstriction in most of the subjects. Because of this potential bronchoconstrictor effect, high doses of oral or intravenous verapamil should be used with caution in asthmatic subjects.

Administration, Inhalation↗
PubMed1992

A discriminant analysis applied to methacholine bronchoprovocation testing improves classification of patients as normal, asthma, or COPD.

UNLABELLED: Two discriminant functions, incorporating baseline measurements of pulmonary function and measures of airway responsiveness, were developed to improve patient classification into groups of normal, asthma, or COPD. Accuracy of group classification was compared between the usual laboratory method (single discriminating cut-off) and these new mathematically developed functions. Forty-five normal subjects, 27 asthmatic patients, and ten well-defined COPD patients were entered into the analysis. Measurements of airway responsiveness were determined by measurement of both specific airway conductance (SGaw) and spirometry (FEV1) after sequential inhalation of methacholine. RESULTS: A single discriminant cut-off using measures of SGaw (PD35) or FEV1 (PD20) does not sufficiently discriminate asthma from groups that contain normal and COPD subjects (67 to 71 percent predictive value). On the other hand, our discriminant functions demonstrated improved patient classification (positive predictive value, 88 to 89 percent). We conclude that bronchoprovocation tests used to evaluate the diagnosis of asthma should incorporate measures of baseline lung function into the analysis. This, we believe, is especially necessary when baseline lung function demonstrates minimal airflow obstruction and the possibility of other causes of airway disease exist.

Adult↗
PubMed1995

Bronchiolitis obliterans in single-lung transplant recipients.

The presentation and clinical course of bronchiolitis obliterans (BO) in single-lung transplant (SLT) recipients has thus far not been well described. We retrospectively analyzed the serial spirometry of 15 SLT patients with BO. All the patients fulfilled the criteria for BO syndrome, and 11 of the 15 had histologically documented BO. Based on serial FEV1 analysis, we identified three patterns of presentation and progression of BO. The first pattern (n = 6) was characterized by a rapid onset and a relentless progressive course; the second pattern (n = 5) was characterized by a similar rapid onset and initial rapid decline, but was followed by stabilization in lung function; the third pattern (n = 4) was characterized by an insidious onset and course. In all patients, a permanent reduction in the mean forced expiratory flow during the middle half of the forced vital capacity appeared to be an early sensitive index for the development of BO. An appreciation of these different modes of presentation and progression of BO is potentially important in the assessment of prognosis and management of the SLT recipient.

Adult↗
PubMed2002

Effects of varying doses of fluticasone propionate on the physiology and bronchial wall immunopathology in mild-to-moderate asthma.

OBJECTIVES: Inhaled corticosteroids (ICS) are typically associated with a flat dose-response curve when traditional efficacy values are examined (eg, FEV(1)). The aim of the present study was to investigate if a dose-response relationship exists for lung function and inflammatory cell numbers in bronchial biopsy specimens. METHODS: Bronchial biopsy specimens were obtained from 36 patients randomized to receive 100 micro g, 500 microg, or 2,000 microg/d of fluticasone propionate (FP). Lung physiology and bronchial biopsies were performed at baseline and after 2 weeks of treatment. RESULTS: Improvement in lung function and suppression of airway inflammation were optimal at a dose of 500 microg/d of FP. Significant changes from baseline following treatment were documented in FEV(1) (p = 0.02), forced expiratory flow (p = 0.002), FEV(1)/FVC (p = 0.007), provocative concentration of histamine causing a 20% fall in FEV(1) (PC(20)) [p = 0.02], T-cell numbers (p = 0.0005), activated eosinophils (p = 0.01), and numbers of macrophages (p = 0.01) in the group treated with 500 microg/d of FP. Comparison between groups administered different doses of FP failed to demonstrate a dose-response relationship for change from baseline in PC(20) (p = 0.43), any of the lung function parameters, T-cell numbers (p = 0.64), activated T cells (p = 0.46), eosinophils (p = 0.53), activated eosinophils (p = 0.48), or macrophage numbers (p = 0.68). CONCLUSION: The apparent lack of a dose-response for ICS treatment in patients with asthma further validates the preferential use of add-on therapy over increasing the dose of ICS.

Adult↗
PubMed2003

Ratio between forced expiratory flow between 25% and 75% of vital capacity and FVC is a determinant of airway reactivity and sensitivity to methacholine.

STUDY OBJECTIVE: The ratio between forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) and FVC is thought to reflect dysanapsis between airway size and lung size. A low FEF(25-75)/FVC ratio is associated with airway responsiveness to methacholine in middle-aged and older men. The current study was designed to assess this relationship in both male and female subjects over a broader range of ages. STUDY DESIGN: Data analysis of consecutive subjects who had a >or= 20% reduction in FEV(1) after <or= 189 cumulative units of methacholine over a 7-year period. SETTING: Pulmonary function laboratory in a university-affiliated hospital. PATIENTS: A total of 764 consecutive subjects aged 4 to 91 years (mean +/- SD age, 40.8 +/- 19.6 years). There were 223 male (29.3%) and 540 female (70.7%) subjects. MEASUREMENTS AND RESULTS: Airway reactivity was assessed as the dose-response slope of the reduction in FEV(1) from baseline vs the cumulative dose of inhaled methacholine. The cumulative dose of methacholine causing 20% reduction in FEV(1) (PD(20)) was used as the indicator of airway sensitivity. In a linear regression model that included age, height, and percentage of predicted FEV(1), the FEF(25-75)/FVC ratio accounted for 7.6% of variability in airway reactivity (p < 0.0001, r(2) = 0.076). Subjects with higher airway sensitivity, indicated by lower PD(20), also had a lower FEF(25-75)/FVC ratio. CONCLUSIONS: A low FEF(25-75)/FVC ratio, indicating small airway size relative to lung size, is associated with higher airway sensitivity and reactivity to methacholine in susceptible subjects.

Adult↗
PubMed1976

Clinical comparison of two electronic spirometers with a water-sealed spirometer.

Two electronic spirometers which use a hot-wire anemometer to measure air flow were clinically compared with a water-sealed spirometer. The forced vital capacity (FVC), the forced expiratory volume in one second (FEV1), the FEV1/FVC%, the mean forced expiratory flow between 200 and 1,200 ml of the FVC, the mean forced expiratory flow during the middle half of the FVC, the mean forced expiratory flow between 75 and 85 percent of the FVC, and the maximum voluntary ventilation were determined for a group of 67 subjects. Techniques are described for connecting the spirometers in series to permit evaluation by human subjects or by syringe injection. High correlation coefficients generally were obtained when comparing the electronic spirometers with the water-sealed spirometer, but the actual range of percent difference was greater than 11 percent in all spirometric tests. The results indicate the need for systematic evaluation of electronic spirometers to characterize their deviation from accented standards. Frequent calibration is necessary to maintain consistent performance.

Adolescent↗
PubMed1978

Aerosol therapy with Sch 1000. Short-term mucociliary clearance in normal and bronchitic subjects and toxicology in normal subjects.

The anticholinergic bronchodilator drug, Sch 1000, was administered as an aerosol by a metered-dose inhaler (200 microgram) to six normal and six bronchitic subjects. The short-term effect on mucociliary clearance was assessed and compared to a placebo (propellant and dispersal agent) in a double-blind crossover study. Mucociliary clearance in the normal group was significantly faster with administration of Sch 1000 than with placebo (P less than 0.01). There was no significant difference between the effects of administration of Sch 1000 and placebo on mucociliary clearance in the bronchitic group. Pulmonary function was significantly increased by therapy with Sch 1000 (as compared to administration of placebo) in the bronchitic group for two hours (P less than 0.05) and in the normal group for one hour (P less than 0.05). In another study, 12 normal subjects inhaled aerosols containing 40 microgram of placebo or 400 microgram of Sch 1000 from metered-dose inhalers on separate days in a randomized double-blind fashion. A significant sustained improvement in pulmonary function (P less than 0.05) and a transient fall in diastolic blood pressure were observed after administration of Sch 1000.

Adult↗