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PubMed1980

Intraregional basis for sequential filling and emptying of the lung.

We studied the sequential pattern of lung filing by measuring the slope of the alveolar plateau in single breath helium washouts after inhaling a bolus at a lung volume (VI) equivalent to 20. 40, 60 and 80% of vital capacity (VC). In seated subjects, prone dogs, both with the chest intact and wide open, and individual canine lobes, slopes at VI = 20% VC were more positive than those at VI = 80% VC, indicating a "first in - last out' pattern. Furthermore the range of slopes, which reflects the magnitude of sequencing, was comparable in the four situations. We conclude that sequential filing and emptying of the lung has predominantly an intraregional basis. A two compartment optimization analysis using single exponential pressure-volume curves suggests that only a small proportion of the lung needs to behave differently to produce the sequencing observed in individual lobes.

Adult↗
PubMed1987

Relationship between maldistribution of ventilation and airways obstruction in children with asthma.

This study was designed to explore the relationship between ventilation non-uniformity, as assessed by moment analysis of nitrogen washout, and airways obstruction, as assessed by spirometry, in children with asthma. Moment ratios derived from the multibreath washout curves in asthmatics were significantly higher than those obtained from healthy controls (P less than 0.001). Among patients with asthma, moment ratios showed a high degree of negative correlations with spirometric variables expressed as percent of predicted, i.e., increasing airways obstruction was associated with increasing ventilation non-uniformity. When the subjects were tested on multiple occasions during one test day the results demonstrated a strong quantitative relationship within subjects between spontaneous changes in moment ratios and spirometric variables (P less than 0.001), with the slope of the regressions showing a trend to vary from one patient to another. Chi squared analysis showed that significant changes in FEV1 were paralleled by corresponding significant changes in moment ratios with a sensitivity of approximately 81% and a specificity of 82%. Additionally, changes in FEV1 induced by an inhaled bronchodilator were associated with concomitant changes in moment ratios. We conclude that: (1) the majority of children with asthma have some degree of ventilation non-uniformity which is correlated with their degree of airways obstruction, and (2) spontaneous changes in airways obstruction in such subjects are paralleled by changes in ventilation non-uniformity.

Adolescent↗
PubMed1976

Clinical and bronchial provocation studies in patients with meatwrappers' asthma.

Reactive airway disease has been meatwrappers employing polyvinyl chloride (PVC) soft wrap film and thermally activated price labels. Sixty-nine percent of 96 meatwrappers responding to a mail survey had work-related respiratory, mucous membrane, or systemic complaints. Smokers developed more pronounced symptoms than nonsmokers. Work-simulated bronchial provocation tests were carried out in 14 symptomatic meatwrappers. Following a 3-hr exposure to polyvinyl chloride fumes, 3 of 11 workers developed a mean decrease of 25% in FEV, and 7 of 11 workers developed a mean decrease of 13 mm Hg in their PaO2. Following a 30-sec to 20-min exposure to price label adhesive fumes, 9 of13 workers developed a mean decrease of 49% in FEV1 and 12 of 13 developed a mean decrease of 20 mm Hg in their PaO2. Though a hypersensitivity reaction to one or more components in PVC or price label adhesive emissions is suspected, the precise pathogenesis of this syndrome remains unknown. The entire spectrum of meatwrappers' syndrome must be interpreted as a complex response to both PVC and price label adhesive fume exposure.

Adult↗
PubMed1977

Bronchodilating activity of an H1 blocker, chlorpheniramine.

The purpose of this study was to test the hypothesis that chlorpheniramine (CP), and H1 blocker, can cause bronchodilatation if administered intravenously (iv) and in higher doses than those currently prescribed. In 10 subjects with allergic asthma, forced expiratory flows (FEF) were recorded on different days, at comparable baseline values, before and up to 5 hr after administration of 8 mg per os (po) chlorpheniramine, 10 mg iv CP (repeated twice), 5.5 mg/kg iv aminophylline, and 30 mg po butabarbital as well as during a day without drug. Chlorpheniramine administered intravenously produced reproducible increases (+ delta) in FEF, starting at 15 min, peaking at 120 min, and still persisting at 5 hr; the peak + delta averaged 15% for FEV1 and 27% to 53% for flows at low lung volume. FEF showed a comparable + delta after aminophylline, a smaller + delta after orally administered chlorpheniramine and no significant + delta during butabarbital or control sessions. The ratio change over time/variability was higher for FEV1, FEF50%, and FEF25%-75% than for the remaining parameters. In six subjects a double-blind study (chlorpheniramine vs. saline solution) confirmed the effectiveness of the doses administered in the open study. In three subjects, 10 mg iv chlorpheniramine was given at four different baseline values; the highest + delta occurred when the basal FEV1 was approximately 50% of the predicted value and the basal FEF at low lung volume 30% to 40% of the predicted value. In two subjects, log dose-response curves to 2.5, 5.0, and 10.0 mg iv chlorpheniramine were obtained by using FEV1, FEF50%, and FEF25%-75%. Thus chlorpheniramine in high iv doses can dilate the bronchi, the + delta FEF depending on the dose, the percent of the predicted basal FEF value, and "individual" responsiveness. Withing the dose range used, bronchodilatation to chlorpheniramine and aminophylline administered intravenously was best detected by FEV1, FEF50%, and FEF25%-75%.

Aminophylline↗
PubMed1994

Pulmonary function in normal non-smoking black southern African adults.

Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory ratio (FEV1/FVC x 100) and forced mid-expiratory flow between 25% and 75% of FVC (FMF) were measured in 3000 lifelong non-smoking Xhosa black Southern African adult population aged 20-60 yr from Umtata in the Transkei in Southern Africa. FVC, FEV1 and FMF were highly correlated with each other and all were highly correlated with age and standing height. The normal ranges for spirometric measurements were narrower than in many previous studies. Mean FVC in the present study was 13% higher than predicted values from other African adults. The present study is the most recent and the largest study of black Africans using the American Thoracic Society 1987 selection criteria of pulmonary function curves and can be used as a reference value for mainly Xhosa black Southern African adult population.

Adult↗
PubMed1995

Salmeterol and formoterol in partially reversible severe chronic obstructive pulmonary disease: a dose-response study.

When testing the response to beta 2-agonist drugs in severe chronic obstructive pulmonary disease (COPD), a dose-response assessment should be undertaken. This study compares the time course of inhaled salmeterol (25, 50 and 75 micrograms) and formoterol (12, 24 and 36 micrograms) at different doses in a group of 12 patients with partially reversible, but severe COPD (FEV1 of 12-32% of predicted values after beta 2-agonist drugs had been withheld for 24 h). All doses of salmeterol and formoterol induced a significant (P < 0.01) spirometric improvement over the 12-h monitoring period, when compared to the spirometric improvement after placebo, but while formoterol induced a dose-dependent increase of the FVC, FEV1 and FEF50, this was not the case for salmeterol. In fact, 75 micrograms salmeterol did not produce a further improvement of these parameters. Mean peak bronchodilation, expressed as the increase in FEV1 over baseline values, occurred 2 h after inhalation of the three doses of salmeterol, and 1 h after inhalation of the three doses of formoterol. A comparison of 50 micrograms salmeterol with 12 micrograms or 24 micrograms formoterol (clinically recommended doses), showed that improvement of FEV1 after salmeterol was statistically (P < 0.05) higher than that after the two doses of formoterol, although the mean peak bronchodilations were similar. This was because salmeterol has a longer duration of action than formoterol. These data demonstrate that salmeterol is equally effective as, but longer-acting than, formoterol at clinically recommended doses in patients suffering from COPD, with severe airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed2005

Changes in induced sputum in the presence of bronchiolitis obliterans syndrome and correlation with spirometry in single and bilateral lung transplant recipients.

Bronchiolitis obliterans syndrome is a clinical diagnosis based on lung function parameters. Using induced sputum, taken from lung transplant recipients, this paper reports on the correlation between the neutrophil count and the percentage change from postoperative baseline for FEV(1), FEF(50), and FEF(25-75). In double lung transplant recipients the correlations were significant for FEV(1) (r = -0.68, p = 0.002), FEF(50) (r = -0.65, p = 0.016), and FEF(25-75) (r = -0.56, p = 0.016). In single lung transplant recipients, no significant correlations were seen.

Bronchiolitis Obliterans↗
PubMed2006

Dry powder inhalation of colistin in cystic fibrosis patients: a single dose pilot study.

BACKGROUND: Dry powder inhalation (DPI) may be an alternative to nebulisation of drugs in the treatment of chest infections in cystic fibrosis (CF) patients. In a pilot study the feasibility of a colistin dry powder inhaler (prototype Twincer) by a single dose in CF-patients was assessed and compared to nebulised colistin. METHODS: Ten CF-patients, chronically infected with P. aeruginosa, participated in a randomised cross over study. On two visits to the outpatient clinic, patients inhaled colistin sulphomethate as 25 mg dry powder (Twincer) or as 158 mg nebulised solution (Ventstream nebuliser, PortaNeb compressor). Pulmonary function tests were performed before, 5 and 30 min after inhalation. Serum samples were drawn prior to each dose and at 15, 45 min, 1.5; 2.5; 3.5 and 5.5 h after inhalation. RESULTS: The DPI was well tolerated by the patients: no significant reduction in FEV1 was observed. Relative bioavailability of DPI to nebulisation was approx. 140% based on actual dose and approx. 270% based on drug dose label claim. CONCLUSIONS: The colistin DPI (Twincer inhaler) is well tolerated and appreciated by CF-patients. Optimisation with respect to particle size and internal resistance of the inhaler is necessary to attain equivalent pulmonary deposition to liquid nebulisation.

Administration, Inhalation↗
PubMed2004

High-resolution computed tomography in young patients with cystic fibrosis: distribution of abnormalities and correlation with pulmonary function tests.

OBJECTIVE: To assess pulmonary abnormalities detected by high-resolution computed tomography (HRCT) in young children with cystic fibrosis (CF) and mild to moderate lung disease. STUDY DESIGN: High-resolution computed tomography was performed in 60 children, 6 to 10 years old, with mild to moderate lung disease (forced expiratory volume in 1 minute [FEV(1)], 52-137; mean, 102; SD, 15% predicted). HRCTs were scored by using a system that evaluates each lobe for severity and extent of CF lung disease. Findings of CF lung disease were tabulated in all subjects and in a subgroup with normal pulmonary function tests. HRCT scores were correlated with FEV(1), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of expired vital capacity (FEF(25-75)) in 57 patients. RESULTS: Bronchiectasis was present in 35% of subjects, mucous plugging in 15%, and air trapping in 63%. No abnormality was detected in 25%. In 37 subjects with FEV(1), FVC, and FEF(25-75) >85% predicted, bronchiectasis was present in 30%. In 17% of these subjects, bronchiectasis was seen in > or =4 lobes. Correlations between HRCT scores and FEV(1) were significant and showed fair to moderate correlation (r=0.36-0.46). CONCLUSIONS: High-resolution computed tomography demonstrated a broad range of pulmonary abnormalities in young patients with CF with mild to moderate lung disease. In this study, abnormalities, including bronchiectasis, were common in young children with CF and normal pulmonary function tests.

Bronchiectasis↗
PubMed2005

Spirometry in the pre-school age group.

Spirometry is a widely used lung-function test in school-aged children and adults. It can also be used to test lung function in the pre-school population, provided that they are tested in a child-friendly setting, by experienced paediatric-orientated personnel and in a way that is congruent with their development. Accurate results can be obtained provided care and attention are paid to applying quality-control criteria suitable for this age group. The biggest challenge is to make the testing fun.

Child, Preschool↗
PubMed2006

Increased hydrogen peroxide concentration in the exhaled breath condensate of stable COPD patients after nebulized N-acetylcysteine.

BACKGROUND: The oxidative burden in the airways is a hallmark of chronic obstructive pulmonary disease (COPD). AIMS: This prospective, cross-over, placebo (PL)-controlled study was designed to investigate the effect of N-acetyl-l-cysteine (NAC) on hydrogen peroxide (H(2)O(2)), nitrites and nitrates (NO(2)(-)+NO(3)(-)), and thiol (RSH) concentrations in exhaled breath condensate (EBC) in stable COPD patients (n=19, aged 52.6+/-15.6 years, 10 females, mean FEV(1) 95.2+/-23.8%, FEV(1)/FVC 69.1+/-11.4%). METHODS: H(2)O(2), NO(2)(-)+NO(3)(-) and RSH concentrations in EBC were determined with homovanillic acid, NADPH-nitrite reductase assays and Ellman's reaction, respectively. RESULTS: Thirty minutes after nebulization, H(2)O(2) concentration increased if levels after NAC (0.45+/-0.25microM) and PL (0.17+/-0.17microM) were compared in COPD patients (p=0.002). This increased H(2)O(2) level in EBC was no longer observed either after 90min: 0.16+/-0.09microM (PL 0.17+/-0.15microM) or 3h: 0.12+/-0.07microM (PL 0.21+/-0.23microM) (p=0.5 and 0.2, respectively). The levels of NO(2)(-) and NO(3)(-) did not differ between NAC and PL. There was no significant difference in RSH levels between nebulized NAC and PL. After nebulized NAC, however, exhaled RSH increased from 1.42+/-1.69microM (0min) to 2.49+/-2.00microM (30min), and 1.71+/-1.83microM (180min) (p=0.009 and 0.03, respectively, compared with 0min). CONCLUSIONS: These data demonstrate that nebulized NAC transiently increases exhaled H(2)O(2) level, whereas it has no effect on other oxidative parameters.

Acetylcysteine↗
PubMed2004

Bronchial hyperreactivity and spirometric impairment in patients with seasonal allergic rhinitis.

UNLABELLED: We previously demonstrated in a group of patients with perennial allergic rhinitis alone, impairment of spirometric parameters and high percentage of bronchial hyperreactivity (BHR). Thus, the present study aimed at evaluating a group of subjects suffering from seasonal allergic rhinitis alone to investigate the presence of spirometric impairment and BHR both during and outside the pollen season. METHODS: One-hundred rhinitics sensitized to pollen allergens only were evaluated during and outside the pollen season. Spirometry and methacholine bronchial challenge were performed. RESULTS: Four rhinitics showed impaired values of FEV1 without referred symptoms of asthma during the pollen season. FEF 25-75 values were impaired in 17 rhinitics during the pollen season and in 11 rhinitics outside the pollen season (P<0.05). Fifty-four patients showed positive methacholine bronchial challenge both during and outside the pollen season. PD20/FEV1 methacholine was lower during the pollen season than outside (P<0.05). In BHR positive patients, reduced values of FVC (P<0.05), FEV1 (P<0.05), and FEF 25-75 (P<0.01) were significantly demonstrated in comparison with BHR negative rhinitics. There was a relationship between BHR degree and FEF 25-75 values only during the pollen season (P<0.001). CONCLUSIONS: This study evidences that an impairment of spirometric parameters may be observed also in patients with seasonal allergic rhinitis alone during the pollen season. A high percentage of these patients had BHR. A close relationship between upper and lower airways is confirmed also in the model of pollen allergy. Thus, a careful evaluation of lower airways should be performed also in those patients with seasonal allergic rhinitis alone.

Adult↗
PubMed2003

Diagnostic value of negative expiratory pressure for airway hyperreactivity.

STUDY OBJECTIVES: To examine the value of negative expiratory pressure (NEP) in the assessment of methacholine bronchoprovocation testing (BPT). DESIGN: Prospective, observational study. SETTING: Pulmonary function laboratory in a university hospital. PARTICIPANTS: Fifty-nine patients with chronic cough referred from outpatient clinics for methacholine BPT. METHODS: Each subject inhaled successive doubling concentrations of methacholine (from 0.049 to 25 mg/mL) until the FEV(1) decreased for > 20% or the maximum concentration of methacholine was inhaled. NEP was measured in the sitting position during tidal breathing before and after methacholine BPT. The FEV(1) and forced oscillation airway resistance (Rrs) and interrupter airway resistance (Rint) were also obtained simultaneously. A positive BPT result was defined as a fall in FEV(1) > or = 20%. RESULT: At baseline, only five patients had expiratory flow limitation as demonstrated by NEP (EFL-N). There were 39 patients with positive BPT results, and the other 20 patients had negative results. Among the BPT-positive patients, only 13 patients (33.3%) had EFL-N after methacholine challenge. The sensitivity indexes (absolute change/SD) of FEV(1), NEP, Rrs, and Rint were 16.0 +/- 9.6%, 1.1 +/- 1.6%, 3.8 +/- 4.5%, and 5.89 +/- 4.4% (mean +/- SD), respectively. The percentage changes in FEV(1) in BPT-positive patients correlated with the percentage changes in Rrs (r = 0.419, p = 0.008) and only marginally with the percentage changes in Rint (r = 0.307, p = 0.058), but not with the changes in EFL-N (r = 0.048, p = 0.77). CONCLUSION: These data suggest that NEP at sitting position is not sensitive in the assessment of methacholine bronchoprovocation as compared to FEV(1) and airway resistance measurements.

Adult↗
PubMed1991

Effects of single- and multiday ozone exposures on respiratory function in active normal children.

Ventilatory function was measured twice daily on 46 healthy children aged 8-14 years on at least 7 days for each child during a 4-week period at a northwestern New Jersey residential summer camp in 1988. The highest 1-hr O3 concentration was 150 ppb, while the highest 12-hr H+ concentration (as H2SO4) was 18.6 micrograms/m3. The highest temperature-humidity index was 81 degrees F. The regressions of FVC, FEV1, FEF25-75, and PEFR on O3 in the hour preceding the afternoon function measurements yielded slopes essentially the same as those measured on other children at the same camp in 1984. Regressions of the changes in function between the late morning and late afternoon function measurements on average O3 concentration between them produced significant, but somewhat smaller effects, while regressions of morning function on O3 during the previous day indicated small but still significant effects. There were no significant correlations with other measured environmental variables including H+. Based on the results of this study and similar previous studies, we conclude that O3 exposures in ambient air produce greater lung function deficits in active young people in natural settings then does pure O3 in controlled chamber exposure studies because of: (1) longer exposures; (2) potentiation by other factors in the ambient exposures; (3) the persistence of effects from prior day's exposures; and (4) the persistence of a transient response associated with the daily peak of exposure. It follows that projections of likely effects in the real world from controlled chamber exposure studies should either have a large margin of safety, or the judgment of the extent of effects likely to occur among populations should be based directly on the effects observed in field studies.

Adolescent↗
PubMed1991

Effect of preoperative stabilization on respiratory system compliance and outcome in newborn infants with congenital diaphragmatic hernia.

To determine whether preoperative stabilization and delay of operative repair of congenital diaphragmatic hernia (CDH) may decrease operative risk, we performed serial pulmonary function tests on 22 newborn infants with CDH and on four infants without pulmonary hypoplasia (two with ileal atresia and two with tracheoesophageal anomalies) who served as control subjects. We used 2 passive respiratory mechanics technique to measure respiratory system compliance. All patients with CDH had respiratory distress immediately after birth, and required mechanical ventilation. Thirteen babies underwent emergency repair (six survived, seven died); nine of them received extracorporeal membrane oxygenation (ECMO) after the operation (two survived, seven died). Operative repair was delayed deliberately for 2 to 11 days in nine infants with severe hypoxemia. Six immediately received ECMO for 4 to 10 days; one died of intraventricular hemorrhage, and five survived and later underwent surgical repair. The seventh patient did not receive ECMO but appeared to have respiratory distress syndrome of infancy and improved after administration of synthetic surfactant. Improvement was seen in two additional infants who received conventional assisted ventilation during a 48-hour delay before surgery, and survived. In all, eight of nine infants who underwent preoperative stabilization survived (p less than 0.05 compared with survival after emergency surgery). Following surgical repair immediately after birth, respiratory system compliance improved only slightly during the first week of life, a time when control infants had a rapid increase in respiratory system compliance (p less than 0.001). In contrast, respiratory system compliance increased nearly twofold in the nine patients undergoing preoperative stabilization (p less than 0.02). Preoperative ECMO was associated with an increase in respiratory system compliance of more than 60% for 1 week, a significant difference from respiratory system compliance among patients undergoing emergency CDH repair (p less than 0.05). These observations provide physiologic evidence of possible benefits of preoperative stabilization before repair of CDH.

Extracorporeal Membrane Oxygenation↗
PubMed1991

Bronchopulmonary dysplasia: improvement in lung function between 7 and 10 years of age.

To evaluate the natural history of bronchopulmonary dysplasia, we studied the same 32 patients at a mean age of 7 and 10 years. The group as a whole had normal height and weight percentiles, and each child grew along his or her established somatic growth curve. Although some children had abnormal values, the group maintained a normal mean total lung capacity and functional residual capacity. The mean residual volume and the residual volume/total lung capacity ratios were elevated at both ages. At age 7 years the 19 patients (59%) who had a forced expiratory volume in 1 second (FEV1) of less than 80% had "catch up" improvement by 10 years of age (65 +/- 11% to 72 +/- 16% of predicted value; p less than 0.05). All the children who had a normal FEV1 at 7 years of age continued to have a normal FEV1 at age 10 years. Resting single-breath carbon monoxide uptake by the lung was normal when measured at age 10 years. The majority of patients had a positive methacholine challenge test result at both ages, although there was a low incidence of clinically diagnosed asthma. This study demonstrates that patients with bronchopulmonary dysplasia who have normal lung function at age 7 have had normal lung growth and that those with evidence of mild to moderate lung disease have continued lung growth or repair, or both, during their school years.

Bronchopulmonary Dysplasia↗