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PubMed1984

Response to cold air hyperventilation in normal and in asthmatic children.

To assess the sensitivity of isocapnic hyperventilation with cold air in detecting airway hyperreactivity in asthmatic children, we studied 13 asthmatic patients (mean age 11.1 years) and 10 normal children. Cold air challenge consisted of 4 minutes of moderate hyperventilation plus another 4 minutes of maximal hyperventilation, both with subfreezing air (-16 degrees to -18 degrees C). Exercise and IHCA tests were done within 5 days and in random sequence. Mean (+/- SE) maximal % delta FEV1 after IHCA was 27 +/- 5.1% in the asthmatic children vs 4.5 +/- 1.2% in the normal subjects (P less than 0.01), even though there were no significant differences in the maximal minute ventilation equivalent between the two groups. Mean maximal % delta FEV1 after exercise was 31.7 +/- 5.6 in the asthmatic group. There was no difference in the sensitivity of the exercise and IHCA tests to detect bronchospasm in asthmatic children. Airway obstruction after IHCA was sharp and brief: maximal at 3 minutes after challenge, and back to 10% of baseline after 11 minutes. In seven asthmatic children the refractoriness to cold air and exercise was studied by repeating each test within 30 minutes; all seven showed significant refractoriness to exercise, and six showed no refractoriness to IHCA. We conclude that exercise and cold air-induced bronchospasm have different physiologic mechanisms, and that cold air testing can be used as a routine challenge to identify airway hyperreactivity in children.

Adolescent↗
PubMed1989

Long-term pulmonary sequelae of meconium aspiration syndrome.

To determine the incidence of long-term sequelae after meconium aspiration syndrome (MAS), we studied 11 children who had MAS at age 8.2 +/- 0.2 years (mean +/- SD) and nine healthy control subjects with pulmonary function and exercise stress tests. The MAS children had evidence of mild airway obstruction, hyperinflation, and increased closing volumes in comparison with control values. During graded exercise stress tests on a treadmill, MAS children achieved normal maximal oxygen consumption and anaerobic threshold without a significant fall in arterial oxygen saturation or increase in CO2 tension. Exercise-induced bronchospasm occurred in four (36%) MAS subjects but in none of the control subjects. We conclude that children surviving MAS have long-term pulmonary sequelae, including airway obstruction, hyperinflation, elevated closing volumes, and airway hyperreactivity; yet they achieve normal aerobic capacity. These findings are similar, although less severe, than those after prematurity and bronchopulmonary dysplasia.

Airway Obstruction↗
PubMed1996

Longitudinal, prospective analysis of dietary intake in children with cystic fibrosis.

OBJECTIVES: Prospective, 3-year longitudinal dietary intakes of 25 prepubertal, pancreatic-insufficient children with cystic fibrosis (CF) and mild lung disease, and the intakes of 26 control children were compared, and relationships among energy intake, nutritional status, and pulmonary function were determined. STUDY DESIGN: Intakes from 3-day weighed food records were compared with CF recommendations, recommended dietary allowances (RDA), and the recommendations of the Third National Health and Nutrition Examination Survey (NHANES III). Energy and nutrient intakes were analyzed by repeated-measures analysis of variance. RESULTS: Children with CF consumed more energy than control children (p = 0.025) in terms of calories per day, percentage of RDA by age and by age and weight, energy adjusted for fat malabsorption, and percentage of NHANES III recommendations. Energy intake was similar between boys and girls with CF. The percentage of energy from fat was greater (p = 0.0004) in the CF group (3-year mean, 33%) than in the control group. Height and weight z scores declined in the CF group (p <0.05) with time. Vitamin and mineral intakes were generally adequate in the CF group. CONCLUSIONS: The children in this sample did not consume the CF recommended intakes of 120% RDA for energy or a high-fat (40% of energy) diet. Energy intakes may be insufficient in this group to meet requirements for optimal growth.

Child↗
PubMed1989

Carbon monoxide diffusing capacity of the lungs determined by single-breath and steady-state exercise methods.

We measured carbon monoxide diffusing capacity of the lungs (DL,CO) by both the resting single-breath (SB) and steady-state (SS) exercise methods in 95 patients referred for pulmonary function testing. A 10-second breath-holding method was used for the SB test. DL,CO (SS) was measured during the last minute of a 3-minute exercise test on a 9-inch step. Results of the two methods showed good agreement, the SB-SS difference averaging -0.70 (SD, 3.39) ml/min per mm Hg. The difference between the two methods was not correlated with other measurements of pulmonary function except minute ventilation during the exercise performed in the DL,CO (SS) procedure. In a separate study of laboratory personnel, the day-to-day variabilities of the two tests were similar (SD, 1.4 ml/min per mm Hg). Alveolar volume obtained by helium dilution during the SB test was comparable to total lung capacity (TLC) estimated by multiple-breath nitrogen washout in patients without severe airway obstruction. In severe airway obstruction, the mean SB alveolar volume was 13.8% less than the TLC by nitrogen washout, a difference that may be useful as an indicator of inefficiency of gas mixing in the lungs. We conclude that the SB and SS exercise methods provide similar estimates of DL,CO in patients referred to a pulmonary function laboratory.

Adult↗
PubMed2003

Flow limitation in infants with bronchopulmonary dysplasia and respiratory function at school age.

Bronchopulmonary dysplasia is associated with abnormalities in lung function during infancy, yet many infants recover with no respiratory problems in the long term. We therefore did a longitudinal study of pulmonary function in 18 children with moderate to severe bronchopulmonary dysplasia. Forced expiratory volume in 1 s (FEV1) and forced mid-expiratory flow (FEF25-75) at school age were lower than normal in 15 of 18 children, and both showed a significant positive correlation with the maximal flow at functional residual capacity (Vmax(FRC)) at 24 months of age (r=0.68 and 0.85, respectively). Our results suggest that assessment of respiratory function during infancy can help to identify children with bronchopulmonary dysplasia at risk of incomplete recovery of respiratory function during childhood.

Bronchopulmonary Dysplasia↗
PubMed2001

Tests of forced expiration and inspiration.

Analysis of the volume versus time curve during a maximum effort forced expiratory vital capacity maneuver started from total lung capacity (TLC) is by far the most performed test of respiratory mechanics, having spread from the laboratory to the wards and outpatient clinics and gradually into the offices of general practitioners. In particular, forced expiratory volume in 1 second (FEV1) is the best characterized test of respiratorv function; information on changes with age, gender, ethnic group, growth and disease is more developed than for any other test, repeatability is good, and it provides useful information across the whole range from normal to advanced disease.

Forced Expiratory Flow Rates↗
PubMed1989

Intrapleural bupivacaine v saline after thoracotomy--effects on pain and lung function--a double-blind study.

The effects of intrapleural (IP) bupivacaine on pain, morphine requirement, and pulmonary function were evaluated in 15 patients for 24 hours after thoracotomy. An IP catheter was placed during surgery. Patients were randomized in a double-blind fashion to receive 1.5 mg/kg of 0.5% bupivacaine IP or saline on two occasions, eight hours apart. A standard anesthetic with thiopental, oxygen, isoflurane, and nondepolarizing muscle relaxant was given. Pain was evaluated with a visual analog pain score every hour, and forced vital capacity (FVC), forced expiratory volume one second (FEV1), peak expiratory flow (PF), and forced expiratory flow 25% to 75% (FEF) were measured 1, 2, 4, 8, and 24 hours postoperatively as well as before and 30 minutes after each IP injection. Arterial blood gases were sampled 1, 2, 8, and 24 hours postoperatively. Plasma bupivacaine concentrations were measured in 10 patients 5, 10, 20, 30, 60, 120, and 180 minutes after IP injection. With each IP bupivacaine injection, the pain score and morphine requirement decreased. There was a significant improvement in all pulmonary function tests in the patients receiving bupivacaine, but no change in the saline controls. The analgesic effect was shortlived (two to five hours), possibly because of loss of bupivacaine in the chest drains. No differences were seen between the two groups after the effect of IP bupivacaine had worn off. Plasma bupivacaine levels had a Cmax of 0.44 to 1.50 micrograms/mL, with a Tmax at 5 to 30 minutes with levels well below 2 to 4 micrograms/mL where increasing toxicity is seen.

Aged↗
PubMed1990

Airway obstruction in asbestos-exposed shipyard workers: with and without irregular opacities.

Airway obstruction was measured by spirometry in 296 boilermakers with 15 or more years shipyard exposure to asbestos. Percent of predicted was used to adjust each worker's pulmonary function values for height (mean 174 cm), age (mean 52.5 years) and cigarette smoking (mean 23.3 years). Mean values were significantly (P less than 0.05) below predicted for FVC 4.23 l 94.2% FEV1 3.06 l 89.3%, FEF25-75 2.51 l sec-1 82.3% and FEF75-85 0.574 l sec-1 77.8%. Corresponding values for the 106 men with pulmonary asbestosis (ILO profusion of opacities 1/0 or greater), were below these levels. Those without radiographic signs of asbestosis had intermediate values significantly below predicted. Correlation coefficients for pulmonary functions with ILO categories of asbestosis (profusion of irregular opacities) were: FVC -0.2381, FEV1 -0.2494, FEF25-75 -0.2403 and FEF75-85 -0.1629. All were significant P less than 0.05. The subgroup with radiographic asbestosis (ILO 1/0 or greater), had more functional loss. Data on this large cohort of asbestos-exposed workers establish that airway obstruction occurs after 15 years of exposure and before the slightest profusion of asbestosis scarring in the lungs of shipyard workers, and worsens progressively with greater profusions of irregular opacities.

Airway Obstruction↗
PubMed1997

Reduced forced expiratory flow in schoolchildren with respiratory symptoms: the Odense Schoolchild Study.

In the present population-based study, spirometric lung function was assessed in symptomatic schoolchildren with and without asthma as compared to an asymptomatic reference group. The primary aim was to investigate if impaired lung function could be demonstrated in symptomatic schoolchildren, even in the absence of diagnosed asthma. Spirometry [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), 50% of forced expiratory flow (FEF 50%) and 75% of forced expiratory flow (FEF 75%)] and anthropometric measures (standing height, weight, skin fold thickness, and length and circumference of the upper arm) were obtained from 1369 8-10-year-old children (81.5% of the eligible population) during the school year 1985-86. In 1321 of those subjects (96.5% of those examined), a self-administered questionnaire was completed. Thirty-five children belonging to ethnic minorities were excluded, thus 1286 subjects were included for further analysis. Point prevalences concerning asthma and respiratory symptoms (wheeze, cough and shortness of breath) were obtained. Thirty-seven children reported asthma and one or more asthma-like symptoms (symptomatic asthmatics), whereas 40 children denied having asthma, although claiming one or more asthma-like symptoms (symptomatic non-asthmatics). In both symptomatic groups, FEF 50% and FEF 75% were reduced relative to the reference group, the deficit being larger in the symptomatic asthmatics. FEF 75% was found to be more reduced than FEF 50%. FEV1 and FVC did not differ significantly between groups. It is concluded that only half of the schoolchildren with respiratory symptoms usually associated with the presence of asthma actually reported having this disease. These results demonstrate the presence of reduced lung function in symptomatic, reportedly non-asthmatic, children, suggesting clinically important underdiagnosis of asthma. More severe impairment of lung function was found in known asthmatics, also implying some degree of undertreatment.

Asthma↗
PubMed2003

Effects of low dose fluticasone/salmeterol combination on surrogate inflammatory markers in moderate persistent asthma.

BACKGROUND: Noninvasive surrogate markers provide valuable information on the asthmatic inflammatory process. We wished to examine the effects of low dose fluticasone/salmeterol combination on different commonly used inflammatory markers in moderate persistent asthma. METHODS: Twenty-five moderate persistent atopic asthmatics were enrolled of whom 20 completed an open label study. Following an initial 4 week steroid washout period in which patients took salmeterol 50 microg dry powder inhaler 1 puff BD, they received the addition of fluticasone as fluticasone 100 microg/salmeterol 50 microg combination dry powder inhaler 1 puff BD for the next 2 weeks. Exhaled nitric oxide, spirometry, methacholine PD20, sputum/blood eosinophils and sputum/serum eosinophil cationic protein (ECP) were measured following the salmeterol only and fluticasone/salmeterol combination treatment periods. RESULTS: Compared to salmeterol alone (i.e. after the steroid washout), the use of fluticasone/salmeterol combination conferred significant improvements (P < 0.05) in all surrogate markers of inflammation apart from serum ECP. Geometric mean fold changes were 4.3-fold/1.3-fold for sputum/blood eosinophils, 2.2-fold/1.2-fold for sputum/serum ECP, 2.3-fold for methacholine PD20 and 1.8-fold for exhaled nitric oxide. CONCLUSIONS: Surrogate markers apart from serum ECP may be used as a guide to evaluate the anti-inflammatory effects of low dose inhaled corticosteroids. Sputum markers tend to be more sensitive than blood when assessing the anti-inflammatory response.

Administration, Inhalation↗
PubMed2003

Relationship of skin-prick reactivity to aeroallergens and hyperresponsiveness to challenges with methacholine and adenosine monophosphate.

BACKGROUND: Clarification of the relationship between atopy and bronchial hyperresponsiveness (BHR), both key features of asthma, is critical to our understanding of the disease. We therefore investigated the putative relationship between skin-prick reactivity to aeroallergens and BHR to direct and indirect stimuli. METHODS: We performed a retrospective analysis of data from 332 patients presenting with a diagnosis of asthma. Patients were characterized by skin prick tests (SPT), spirometry and bronchial challenge with methacholine and adenosine monophosphate (AMP). RESULTS: For patients who had BHR to methacholine but not AMP, the presence of atopy was associated with a lower PD20 (the provocative dose of methacholine producing a fall in FEV1 of 20%), amounting to a geometric mean (95% confidence interval (CI)) of 2.3-fold (1.4-4.0) difference. Furthermore, the number of skin-prick positive (SPP) responses was related to methacholine reactivity: 0-1 SPP, PD20 = 69.9 micro g; 2-4 SPP, PD20 = 47.8 micro g; 5-8 SPP, PD20 = 35.6 micro g. There was a 2.0- fold (1.1-3.6) difference between the groups with a low (0-1 SPP) and high (5-8 SPP) degree of skin-prick reactivity. A similar pattern was seen when data were analyzed including only perennial allergens. Spirometry was unrelated to the degree of skin-prick reactivity. DISCUSSION: These results suggest that skin-prick reactivity to aeroallergens is associated with BHR to methacholine.

Adenosine Monophosphate↗
PubMed2000

Performance of forced expiratory manoeuvre in children.

The negative expiratory pressure (NEP) method has been previously used to assess the performance of forced vital capacity (FVC) manoeuvre in normal adults. The aim of the present study is to assess whether flow limitation is achieved during FVC manoeuvres in children aged 6-14 yrs. NEP (-10 cmH2O) was successfully applied in 177 normal children, the portion of FVC over which expiratory flow did or did not change with NEP being taken as effort-dependent and effort-independent, respectively. In all children peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) increased with NEP, indicating that PEF was in the effort-dependent portion of FVC. This portion decreased significantly with age (50-20% of FVC from 6-14 yrs). It is suggested that this mainly reflects the poorer coordination of specialized motor acts in younger children because of incomplete morphological and functional maturation of the relevant central nervous system (CNS) mechanisms. The results indicate that most unexperienced children aged 6-14 yrs can perform acceptable forced vital capacity manoeuvres, eventually achieving flow limitation over a portion of the forced vital capacity that increases with age. The negative expiratory pressure method can be used for online assessment of the performance of forced vital capacity manoeuvres and evaluation of treatment-related effects.

Adolescent↗
PubMed2006

Oral magnesium supplementation in asthmatic children: a double-blind randomized placebo-controlled trial.

OBJECTIVE: To investigate the long-term effect of oral magnesium supplementation on clinical symptoms, bronchial reactivity, lung function and allergen-induced skin responses in children and adolescents with moderate persistent asthma. DESIGN: A double-blind randomized parallel placebo-controlled study. SETTING AND SUBJECTS: The patients were recruited from the Pediatric Outpatient Clinic, Division of Pulmonology, Allergy and Immunology, and followed at the Center for Investigation in Pediatrics at State University of Campinas Hospital, Brazil. Thirty-seven out of 72 patients met the study criteria. There were no dropouts. INTERVENTION: The 37 patients (aged 7-19 years, 19 males) were randomized in two groups: magnesium (n=18, 300 mg/day) and placebo (n=19), during 2 months. Both patient groups received inhaled fluticasone (250 microg twice a day) and salbutamol as needed. The primary outcome was bronchial reactivity evaluated with methacholine challenge test (PC20). RESULTS: After a follow-up of 2 months, the methacholine PC20 for testing bronchial reactivity has augmented significantly in the magnesium group only. The skin responses to recognized antigens have also decreased in patients treated with magnesium. The forced vital capacity (FVC), the forced expiratory volume at first second (FEV1), the forced expiratory flow at 25-75 and the FEV1/FVC ratio were similar in both groups. The magnesium group presented fewer asthma exacerbations and used less salbutamol compared to the placebo group. CONCLUSIONS: Oral magnesium supplementation helped to reduce bronchial reactivity to methacholine, to diminish their allergen-induced skin responses and to provide better symptom control in pediatric patients with moderate persistent asthma treated with inhaled fluticasone.

Adolescent↗
PubMed2003

Effect of the second-generation antihistamine, fexofenadine, on cough reflex sensitivity and pulmonary function.

AIMS: Current guidelines recommend the use of first-generation antihistamines for the treatment of cough due to rhinitis/postnasal drip syndrome. The antitussive activity of the second-generation antihistamine, fexofenadine, has not been investigated. Therefore, we evaluated the effect of fexofenadine on capsaicin-induced cough in healthy volunteers and in subjects with acute viral upper respiratory tract infection (URI). METHODS: Twelve healthy volunteers and 12 subjects with URI underwent pulmonary function testing and capsaicin cough challenge on two separate days, 2 h after ingesting 180 mg fexofenadine or matched placebo. Subjects inhaled single, vital-capacity breaths of capsaicin aerosol, administered in incremental doubling concentrations, until the concentration inducing five or more coughs (C5) was determined. RESULTS: In both subject groups, C5 was not significantly different after fexofenadine compared to placebo. In subjects with URI, pulmonary function studies were also similar. In healthy volunteers, however, FEV1 and FEF(25-75), pulmonary function parameters reflecting the degree of airway dilatation, were significantly increased after fexofenadine. Mean (95% CI) values for FEV1(L) after fexofenadine and placebo were 3.16 (2.77, 3.55) and 3.08 (2.69, 3.47), respectively (P = 0.017). Mean values for FEF(25-75)(L/s) were 3.49 (3.10, 3.88) and 3.26 (2.79, 3.72), respectively (P = 0.029). CONCLUSIONS: Fexofenadine demonstrated no antitussive activity against capsaicin-induced cough in healthy volunteers and subjects with URI. The ineffectiveness of fexofenadine in suppressing cough probably reflects the lack of anticholinergic activity and central nervous system penetrance that is characteristic of first-generation antihistamines. The mild bronchodilation induced by fexofenadine in healthy volunteers is of unclear clinical significance and requires further investigation.

Adolescent↗
PubMed1998

Serum eosinophil cationic protein as a marker of eosinophilic inflammation in asthma.

BACKGROUND: The serum level of eosinophil cationic protein (ECP) has been used as a clinical marker in asthma, on the assumption that it reflects ongoing eosinophilic inflammation of the airways. However, only a few studies have investigated this issue, using bronchial secretions but not tissue specimens. OBJECTIVE: To evaluate cross-sectionally the correlation between serum ECP level or blood eosinophil count, and the degree of eosinophilia in bronchoalveolar lavage fluid (BALF) and bronchial biopsy tissue, and disease activity, in asthmatic patients. METHODS: Thirty-three adults with symptomatic asthma and six healthy controls were studied. The blood eosinophil count, ECP levels in serum and BALF, percentage of eosinophils in BALF, number of eosinophils in bronchial tissue, pulmonary function, and methacholine bronchial responsiveness of these subjects were clarified. An asthma severity score and inhaled beta2-agonist requirement (puffs/day) were also assessed for the asthmatic patients. RESULTS: The asthmatic patients, compared with the controls, had more obstructive (as tested by %FEV1, FEV1/FVC, and FEF25-75%) and more responsive airways, and showed a significant increase in the number of eosinophils in the blood, BALF, and tissue, and in the serum ECP levels. The ECP levels in BALF were below the detection limit for most of the subjects in both groups examined. In the asthmatic patients, serum ECP level demonstrated correlations with the number or percentage of eosinophils in BALF and tissue, whereas the blood eosinophil count correlated only with the percentage of eosinophils in BALF. Serum ECP level correlated with all indices of disease activity examined; %FEV1, FEV1/FVC, FEF25-75% bronchial responsiveness, severity score and beta2-agonist usage, whereas the blood eosinophil count correlated only with %FEV1 and bronchial responsiveness. CONCLUSION: The data suggest that serum ECP level reflects the intensity of eosinophilic airway inflammation, as well as the disease activity, and may be useful as an inflammatory marker in asthma.

Adult↗
PubMed2003

Eosinophils from patients with asthma express higher levels of the pan-leucocyte receptor CD45 and the isoform CD45RO.

BACKGROUND: Eosinophils and their secreted mediators are heavily implicated as effector cells in asthma and other allergic diseases. Comparisons were made between expression of CD45, CD45RA, CD45RB and CD45RO by eosinophils from asthmatic patients and non-asthmatic atopic and non-atopic, non-asthmatic control subjects. METHODS: Twenty-seven patients with asthma and 33 control subjects were recruited for the study. Eosinophil expression of CD45, CD45RA, CD45RB and CD45RO was established by immunostaining and flow cytometry was performed on whole leucocyte samples. Eosinophil apoptosis in response to CD45 and CD45 isoform monoclonal antibody (mAb)-dependent receptor ligation was assessed by binding of annexin V and flow cytometry. RESULTS: Eosinophils from patients with asthma expressed significantly (P<0.05) higher levels of pan-CD45 and CD45RO compared with eosinophils from non-asthmatic, non-atopic subjects. No significant correlations were found between expression of either pan-CD45 or CD45RO and the degree of symptoms in the asthmatic patients as defined by lung function (FEV1 and FEF25-75) and methacholine PD20. Increased expression of pan-CD45 or CD45RO did not appear to be a consequence of the atopic phenotype. Higher expression of pan-CD45 or CD45RO by eosinophils from asthmatic patients was not associated with greater sensitivity to CD45 and CD45RO mAb receptor ligation-induced eosinophil apoptosis. CONCLUSION: Higher expression of CD45 and CD45RO by eosinophils from asthmatic patients appeared to be a consequence of asthma rather than atopy and further supports a role for activated eosinophils in asthma.

Adolescent↗