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Does the supine position worsen respiratory function in elderly subjects?

The aim of our study was to test whether the supine position or the sitting position worsens static, forced expiratory flows and measurements of lung mechanics in a group of aged subjects living in a nursing home who were clinically stable and without clinical evidence of cardiorespiratory diseases. Seventeen subjects (mean age 80 +/- 7 years; 16 f) were studied under baseline conditions. Spirometric, breathing pattern and mechanics data by means of an esophageal balloon were measured in sitting and supine positions. Analysis of sitting results showed aged subjects to have a slight flow limitation in peripheral airways, an increase in expiratory airways resistance and mild hyperinflation index (PEEPi = 2.2 +/- 1.9 cm H2O). Pressure time index did not reach the fatigue level in hardly any patient. Maximal inspiratory pressure values (42 +/- 15 cm H2O) were reduced by about 50% in comparison with our normal laboratory standards. Arterial blood gas analysis revealed no pathological data in any subject. When supine, subjects revealed a significant decrease in forced expiratory volume at the first second (p < 0.005), in forced vital capacity (p < 0.01) and in peak expiratory flow (p < 0.05). Moreover, mechanics and breathing pattern data showed a significant decrease in tidal volume (Vt) and dynamic lung compliance (Cld) (p < 0.05) and an increase in respiratory rate/Vt ratio (p < 0.05). Our data confirm the results of previous reports about Cld decrease in supine posture in young normal people. Although our aged subjects showed a significant decrease in forced expiratory volumes and Vt when the supine position was adopted, static mechanics data did not appear modified by the gravitational effect of this posture.

Aged↗

Changes in residual volume during induced bronchoconstriction in healthy and asthmatic subjects.

The increase of residual volume (RV) was investigated during acute bronchoconstriction induced in healthy subjects by methacholine (MCh) (Group 1, n = 13) and in asthmatics by MCh (Group 2, n = 21), or housemite dust (Group 3, n = 11) during early and late airway responses (EAR and LAR), or a series of deep breaths (Group 4, n = 7). In all subjects the difference between residual volume after partial (RVp) and maximal maneuver (RV), expressed as a percentage of control FVC, increased during bronchoconstriction and was correlated with the percent increase of maximal to partial flow ratio at 50% of control FVC (M/P50) (r = 0.854, p < 0.0001). At comparable reduction of partial expiratory flow at 50% of control FVC (VP50), the decreases of FEV1 and FVC were less in healthy than asthmatic subjects, whereas the change of FEV1/FVC was similar in all groups, reflecting similar change in slope of flow-volume curves. The increase of RVp was similar in all groups (range: 15 to 19%), but the increase of RV was 6 +/- 1% (SEM) in healthy subjects and significantly greater (range: 11.1 to 13.3%) in all groups of asthmatics (p < 0.02, analysis of variance [ANOVA]). The effect of deep inhalation (DI) on the airway caliber as assessed by the increase of M/P50 was higher in normal subjects than in all groups of asthmatics (p < 0.0001). A negative correlation was found between the increases of RV and M/P50 in all groups (r = -0.358, p < 0.01), suggesting that healthy subjects had a limited increase of RV because of a marked bronchodilator effect of DI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A new technique to generate and assess forced expiration from raised lung volume in infants.

We have developed a new technique that allows assessment of infant lung function over an extended volume range. The lungs are rapidly inflated to a predetermined inflation pressure (PP) using a modified diaphragm pump. Forced expiratory flow-volume (FEFV) curves are then generated from raised lung volumes using an inflatable plastic jacket. We studied 26 normal infants with a median age of 14 mo (range, 3 to 23 mo). FEFV curves were obtained in each infant from end-tidal inspiration and from lung volumes set by a range of PP (15 to 20 cm H2O). Mean (SE) volume above FRC was 107 ml (9 ml), and mean forced expiratory time was 0.73 s (0.05 s) at end-tidal inspiration. Both measurements increased progressively with increases in PP to 251 ml (13 ml) and 1.04 s (0.06 s), respectively, at 20 cm H2O PP (p < 0.0001). Mean intrasubject coefficient of variation was 15.5% (95% confidence interval, 12 to 19%) for maximal flow at FRC, but it was less than 6% (95% CI, 4 to 8%) for forced expiratory volume-time (FEVt) measurements at all levels of PP. Twenty-seven recurrently wheezy infants with a median age of 13 mo (range, 6 to 18 mo) were subsequently studied using a PP of 17.5 cm H2O. Wheezy infants had a lower VmaxFRC [mean (1.39 ml/s/cm) and 95% CI (1.15 to 1.63 ml/s/cm)] than did normal infants (1.78 ml/s/cm; CI, 1.51 to 2.05) (p < 0.05). FEV1 measurements were all lower in wheezy infants than in normals infants: mean FEV0.5, 1.86 ml/cm (CI, 1.73 to 1.98) and 2.31 ml/cm (CI, 2.15 to 2.48), respectively (p < 0.0001); FEV0.75, 2.20 ml/cm (CI, 2.07 to 2.32) and 2.72 ml/cm (CI, 2.52 to 2.91), respectively (p < 0.0001); FEV1.0, 2.42 ml/cm (CI, 2.26 to 2.58) and 2.84 ml/cm (CI, 2.63 to 3.06), respectively (p < 0.005). The Ci values of each FEVt measurement did not overlap between the wheezy and normal groups; however, the CI values of VmaxFRC overlapped markedly. In addition, FEVt parameters showed greater sensitivity in detecting reduced lung function (71 to 89%) than did VmaxFRC parameters (56%). We conclude that (1) FEVt measurements derived from a lung volume set by a standardized pressure are more reproducible than flow measurements in the tidal volume range; (2) FEVt measurements are significantly lower in wheezy infants than in normal infants, show less overlap than flow measurements in the tidal volume range, and therefore are better able to separate the two populations.

Forced Expiratory Flow Rates↗

The effect of inhaled nitric oxide in pediatric asthma.

Nitric oxide (NO) appears to play an important role in regulating several biologic functions in the lung, including modulation of pulmonary arterial and bronchial smooth muscle tone. Recent studies have shown that relatively high concentrations of inhaled NO reduce the bronchoconstrictor effect of methacholine in animal models. This raises the possibility that NO inhalation might have therapeutic potential as an alternative bronchodilator. Although investigation of this potential in adults with airway reactivity or bronchial asthma has been reported, data are lacking on the role of NO in the pediatric asthma population. We therefore performed spirometry on 12 children with asthma (mean age 11.1 yrs) at baseline (B), immediately after inhaling 40 ppm NO (NO-1), 10 min after inhaling NO (NO-10), and after inhalation of a standard beta 2-agonist, albuterol (A). Baseline pulmonary functions (% predicted +/- SEM) were FVC of 103.2 +/- 5.6, FEV1 of 82.2 +/- 3.3, FEF-max of 97.0 +/- 3.6, and FEF25-75% of 53.5 +/- 3.3. There were no statistically significant differences between baseline and NO-1 or NO-10 between any of the four pulmonary function parameters measured. Inhaled albuterol, however, resulted in significant improvement (% predicted +/- SEM) in FVC to 109.8 +/- 3.5, FEV1 to 99.7 +/- 2.9, FEFmax to 106.5 +/- 5.1, and FEF25-75% to 84.4 +/- 6.4 compared with the baseline and NO inhalation groups. We conclude that NO inhaled at 40 ppm has no apparent bronchodilatory effect in pediatric subjects with asthma and mild airways disease. The clinical application of this gas as a therapeutic modality under these conditions is questionable.

Administration, Inhalation↗

Methacholine responsiveness using the raised volume forced expiration technique in infants.

Infant lung function can be assessed with the tidal volume "squeeze" technique or, over an extended volume range, with the newer raised volume forced expiration technique (RVFET). We assessed methacholine responsiveness in 11 infants, measuring both maximal expiratory flow at functional residual capacity (V.max,FRC)with the tidal volume technique, and forced expiratory volume/time (FEV(t)) with RVFET. We used a standard methodology for the former. FEV(t) was measured by inflating the infant's lungs to 20 cm H2O and forcing expiration using a jacket setup to transmit a pressure of 20 cm H2O to the airway. Lung function was measured at baseline and after methacholine inhalations, increasing from 0.1 g/L to 10 g/L in half log dosage increments (DI). The provocative concentrations (PC) of methacholine leading to a 40% fall in V.max,FRC and a 15 or 20% fall in FEV(t) were calculated. The mean provocative concentration of methacholine required to produce a 40% fall in V.max,FRC was less than that required to produce a 20% fall in FEV0.5 by 0.39 DI (95% CI, -0.60 to 1.38) and less than that required to produce a 20% fall in FEV0.75 by 0.42 DI (95%, CI, -0.54 to 1.39). Similarly, the provocative concentration of methacholine required to produce a 40% fall in V.max,FRC was less than that required to produce a 15% fall in FEV0.5 by 0.14 DI (95% CI, -0.99 to 1.28) or a 15% fall in FEV0.75 by 0.13 DI (95% CI, -0.80 to 1.08), but the differences were small and not significant. Despite these differences the agreement between the two methods was good, and bronchoconstriction was not attenuated by the forced inspiration delivered by the raised volume maneuver. We conclude that the raised volume forced expiration technique is able to detect methacholine-induced bronchoconstriction.

Bronchial Provocation Tests↗

Dose-related reversal of acute lung rejection by aerosolized cyclosporine.

This study evaluated the effectiveness of aerosolized cyclosporine as rescue therapy for refractory acute rejection in lung-transplant patients that is unresponsive to conventional therapy. Over 2 yr, nine allograft recipients with histologic evidence of persistent acute rejection and worsening pulmonary function were enrolled. Twenty-two patients with similar degrees of unremitting rejection served as historical controls. Aerosolization of cyclosporin A (300 mg in 4.8 ml propylene glycol) using an AeroTech II jet nebulizer was instituted daily for 12 consecutive days followed by a maintenance regimen of 3 d/wk. Cyclosporine and tacrolimus blood and plasma levels were maintained within therapeutic ranges throughout this trial. Efficacy was assessed by histologic grade of rejection, interleukin-6 (IL-6) mRNA expression by graft bronchoalveolar lavage cells, and pulmonary function testing before and during cyclosporine therapy. In seven patients, results were correlated to deposition of cyclosporine aerosol in the allograft(s) as measured by radioisotopic techniques. At a mean of 37 d after initiation of aerosolized cyclosporine, graft histology improved in eight of the nine patients. Cellular IL-6 mRNA expression decreased significantly in seven patients (mean IL-6/actin +/- SD, 40.96 +/- 118 versus 0.33 +/- 0.57 [p = 0.038]). Pulmonary function (FEV1), which had decreased posttransplant (over a mean of 347 d of observation) from a best value of 1.98 +/- 0.8 L to 1.59 +/- 0.6 L (p = 0.0077), improved over time (152 d) to a posttransplant value of 1.90 +/- 0.8 (p = 0.025). In the control subjects, FEV1 inexorably declined over a comparable period of observation (best posttransplant value 2.36 +/- 0.86 to 1.32 +/- 0.53, p < 0.0001). There was a strong correlation between cyclosporine deposition in the allograft and improvement in FEV1 (r = 0.900, p < 0.01). Fewer cycles of pulsed corticosteroids (1.4 +/- 0.9 versus 0.2 +/- 0.4, p = 0.011) and anti-thymocyte globulin 0.8 +/- 0.4 versus 0, p = 0.018) and reduced doses of oral prednisone (10.8 +/- 3.1 versus 6.1 +/- 4.2 mg/d, p = 0.026) were observed during treatment with aerosolized cyclosporine. Episodes of pneumonia also were reduced significantly during aerosol therapy (2.6 versus 0.95 episodes/100 d, p = 0.029). Nephrotoxicity and hepatotoxicity did not occur, and no patients withdrew from the study. Aerosolized cyclosporine appears to be safe and effective therapy for refractory acute rejection, but confirmation by a larger, randomized trial is necessary. The correlation observed between deposition of cyclosporine aerosol and physiologic improvement of lung function suggests that there is a dose-response relationship between the concentration of cyclosporine in the allograft and immunologic tolerance.

Acute Disease↗

Detection of expiratory flow limitation by manual compression of the abdominal wall.

We have assessed a new method, manual compression of the abdominal wall (MCA) during expiration, in the detection of expiratory flow limitation. Twelve stable patients with chronic obstructive pulmonary disease (COPD) and five normal subjects were studied during spontaneous breathing in the supine and seated posture. MCA was performed during expiration with one hand at the umbilical level and we measured flow, volume, pleural (Ppl) and gastric (Pga) pressures and abdominal anteroposterior (AP) diameter at the umbilical level with magnetometers. No increase in expiratory flow during MCA relative to the preceding breath despite associated increases in pressures was considered as indicating expiratory flow limitation. In seven additional patients with increased upper airway collapsibility (obstructive sleep apnea syndrome [OSAS]), MCA was compared with negative expiratory pressure (NEP). In normal seated subjects, MCA was associated with a decrease in abdominal AP dimension (mean +/- SD: -27 +/- 6%), an increase in Pga (14.7 +/- 7.4 cm H(2)O) and Ppl (6.2 +/- 2.2 cm H(2)O), and an increase in expiratory flow. MCA caused similar changes in abdominal AP dimension and pressures in seated patients with COPD but six of them (50%), including four patients with FEV(1) less than 1 L, had no increase in expiratory flow. In the supine posture, MCA always increased expiratory flow in normal subjects but four additional patients with COPD showed evidence of flow limitation. MCA invariably increased expiratory flow in patients with OSAS whereas the NEP method suggested flow limitation in some cases. We conclude that MCA is a very simple method that allows detection of flow limitation in different positions.

Abdominal Muscles↗

Reduced airway distensibility, fixed airflow limitation, and airway wall remodeling in asthma.

The airways of individuals with asthma are less distensible than normal and it has been assumed that this may be due to airway remodeling associated with chronic inflammation, although there are currently no available data directly relating these two aspects of asthma. We have therefore carried out a study of the relationship between airway distensibility (DeltaVD) and subepithelial reticular basement membrane (RBM) thickening as an index of airway remodeling, in a group of patients with relatively mild but symptomatic asthma. Our methods included a cross-sectional study of DeltaVD in patients with mild to moderate atopic asthma, with matched airway biopsy for structural components. We confirmed that DeltaVD was lower in patients with asthma than in normal individuals (19.8 +/- 1.1 versus 24.1 +/- 1.5; p < 0.05) and that RBM thickness was increased in patients with asthma (9.1 +/- 2.2 versus 7.7 +/- 1.2 microm; p < 0.01). There was a negative correlation between DeltaVD and RBM thickness in asthma (r = -0.37, p = 0.03) and positive correlations between percent predicted postbronchodilator large and small airway function (for percent predicted FEV(1 )versus DeltaVD, r = 0.59, p < 0.001). We conclude that, cross-sectionally, DeltaVD was related to airway remodeling (RBM thickening) and airflow limitation (percent predicted large and small airway function). Our findings support the hypothesis that DeltaVD is a physiologic test that is reflective of airway remodeling.

Adult↗

Cholinergic-mediated bronchoconstriction induced by prostaglandin D2, its initial metabolite 9 alpha,11 beta-PGF2, and PGF2 alpha in asthma.

In this study, we have investigated the contribution of cholinergic-mediated bronchoconstriction in the airway response provoked by inhaled prostaglandin (PG)D2, its metabolite 9 alpha, 11 beta-PGF2, and PGF2 alpha, which are generated during mast cell activation in vivo and are potent bronchoconstrictor agonists in humans. The effect of prior inhalation of 1 mg ipratropium bromide (IB) on the bronchoconstrictor response to inhaled methacholine (MCh), PGD2, 9 alpha, 11 beta-PGF2, and PGF2 alpha was determined in 7 allergic asthmatic subjects by measuring changes in SGaw, FEV1, and Vmax30. Methacholine, PGD2, and 9 alpha, 11 beta-PGF2 caused concentration-related bronchoconstriction with PGD2 and 9 alpha, 11 beta-PGF2 being between 45 and 112 times more potent than MCh (p less than 0.05), depending on the method used to measure airway caliber. Preinhalation of IB displaced the concentration response curves to MCh between 69- and 196-fold to the right, and this was significantly greater than that observed with PGD2 (12- to 23-fold, p less than 0.02) and 9 alpha, 11 beta-PGF2 (12- to 22-fold, p less than 0.02). Ipratropium bromide inhibited the bronchoconstriction achieved with the highest concentration of agonist by 73 to 91% with MCh, 46 to 79% with PGD2, and 32 to 38% with 9 alpha, 11 beta-PGF2. Ipratropium bromide did not affect the bronchoconstriction pattern to inhaled PGF2 alpha, irrespective of the nature of the response. We conclude that although PGD2 and 9 alpha, 11 beta-PGF2 are potent contractile agonists of human smooth muscle in vitro, bronchoconstriction observed with these mediators in vivo results from a combination of both direct and cholinergic-mediated mechanisms.

Adult↗

Spirometric abnormalities in young smokers correlate with increased chemiluminescence responses of activated blood phagocytes.

Spirometric values determined from the flow-volume loops of 60 healthy young smokers (mean age, 28 +/- 0.6 yr) were correlated with measurements of the release of extracellular and intracellular reactive oxidants (RO) as determined by luminol-enhanced chemiluminescence (LECL) from peripheral blood activated with the synthetic chemotactic tripeptide FMLP combined with cytochalasin B (CB). Fractionation and reconstitution experiments revealed that LECL originated predominantly from polymorphonuclear leukocytes (PMNL). Circulating total leukocyte counts and serum thiocyanate levels were also determined. The data were analyzed using Spearman's correlation coefficient and by multiple regression analysis. Cigarette smoking was associated with elevated intracellular and especially extracellular LECL responses, the latter being strongly correlated (p less than 0.0001) with cigarettes smoked per day, serum thiocyanate levels, circulating leukocytes, and PMNL counts. Abnormalities of the spirometric parameters FEV1/FVC, FEF50/FVC, FEF25, FEF25-75, and FEF75-85 correlated best with extracellular LECL (p less than 0.0002 to p less than 0.0001), but also with pack-years (p less than 0.006 to p less than 0.0001), cigarettes smoked per day (p less than 0.008 to p less than 0.0002), thiocyanate levels (p less than 0.04 to p less than 0.002) and leukocyte counts (p less than 0.03 to p less than 0.002). According to stepwise multiple regression analysis of the data the combination of the independent variables extracellular LECL, pack-years, and numbers of circulating PMNL accounts for 35.6% of the variation in lung function in the group of cigarette smokers, with LECL being the most important contributor (26%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Acute lower respiratory illness in childhood as a predictor of lung function and chronic respiratory symptoms.

This study investigated the relationship of acute lower respiratory illness (LRI) to level and change in level of forced expiratory volumes in a cohort of 801 children, followed longitudinally for a maximum of 13 yr. The co-occurrence of respiratory illness before 2 yr of age and two or more LRI during a single surveillance year was associated with a 20.3% lower mean cross-sectional level of FEF25-75, and with reduced longitudinal change in level of FEF25-75. The effect of LRI on lung function was uniformly stronger for boys than for girls. Of the children with illness before 2 yr of age and two or more LRI, six of 14 were male asthmatics with mean levels of FEF25-75 that were lower than those of other asthmatic children. Pneumonia and/or hospitalization for respiratory illness prior to the onset of study were associated with lower cross-sectional levels of forced expiratory volumes at entry to the study, even when asthmatics/persistent wheezers were eliminated from the analysis (6.1% lower level of FEV1 for a nonasthmatic boy with previous hospitalization versus a nonasthmatic boy without hospitalization). In the longitudinal analysis, pneumonia and/or hospitalization were associated with slower increase in level of forced expiratory volumes, even after adjusting for "ever diagnosis of asthma/current any wheeze" (starting at the same leve, after eight years a boy with hospitalization would develop a 5.0% lower FEV1 than a boy without hospitalization). Acute LRI also was evaluated as a predictor of chronic respiratory symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Variation of breath sound and airway caliber induced by histamine challenge.

Inspiratory breath sounds were recorded from the chest wall during histamine challenge in five subjects with mild asthma (baseline FEV1 greater than 60% of predicted normal). The median frequency of the power spectrum of the breath sounds was found to correlate with the percentage change in FEV1 induced by histamine and with FEF50. The analysis suggests that for a decrease in FEV1 of 20%, the median frequency of breath sound would increase by 80 Hz. Variation in airway caliber produced a consistent alteration in the distribution of energy in inspiratory breath sound in the absence of wheeze. Spectral analysis of breath sound may be a useful addition to conventional spirometry in identifying changes in airway diameter.

Adult↗

Comparisons of spirometric reference values and the proportions of abnormal subjects among male smokers and those symptomatic in a community population.

A comparison was performed of various population reference equations for several spirometric measurements. The objective was to determine if the different equations yielded similar distributions of the percent predicted values, similar reference values for asymptomatic nonsmokers (i.e., normal subjects), criteria (or cutoff points) for who might be defined statistically as normal, and similar proportions of smokers and symptomatic subjects who would fall below the criteria values and thus be considered statistically abnormal. The cross-sectional study population of adults in Tucson, subjects of an ongoing study, was used. Most of the equations yielded reasonably similar distributions of percent predicted values. Older and/or more unusual equations did not yield similar results. Using the lower 95th percentile criteria yielded similar cutoff points as reference values for statistical normality, and similar proportions of statistically abnormal among various smoking and symptomatic groups; some of the equations used did not. When the criteria used were the lower 1.645 SEE, or the published criteria, the proportions considered statistically abnormal were very low or very high; again, some equations gave very disparate results. The first conclusion was that the use of the lower 95th percentile criteria was more sensitive and specific. It was concluded also that most equations yield sufficiently similar results such that the choice of reference equation from those available would depend on other criteria.

Adult↗

Bronchial responsiveness to histamine in infants and older children.

Normal infants have been shown to respond to a relatively low concentration of inhaled histamine. However, those studies used partial maximal expiratory flow volume (PMEFV) curves to assess lung function. In order to directly compare responsiveness between infants and older children, we compared bronchial responsiveness to histamine between a group of 45 normal infants, median age 4 wk (range 2 to 6 wk) and a group of 30 nonasthmatic older children, median age 10 yr (range 5 to 15 yr) using PMEFV curves in both groups to assess lung function. In the infant group, PMEFV curves were generated using the forced expiratory flow volume technique. For the older children, PMEFV curves were generated by voluntary effort. The provocative concentration of histamine that produced a 40% fall (PC40) in maximum flow at functional residual capacity (VmaxFRC) was calculated from the PMEFV curves. The geometric mean PC40 of the infants (1.02 g/L) was lower than the geometric mean of the older children (3.4 g/L) (p less than 0.001). However, these results were then corrected for dilution of the aerosol due to air entrainment (AE). Corrected values of PC40 were not significantly different between infants and older children. These results demonstrate the importance of accounting for AE in the evaluation of histamine responsiveness and suggest that bronchial responsiveness may be similar in normal infants and older children.

Adolescent↗

Increase in airway responsiveness and effect of deep inhalation on airway caliber in allergen-induced asthma. Relationship to the late-phase response.

The airway responsiveness to methacholine (MCh) and the effect of deep inhalation (DI) on airway caliber were determined in 18 asthmatic patients at baseline and 3 and 24 h after an allergen inhalation challenge. The dose of MCh causing a 20% fall of FEV1 (PD20) was used as an index of airway responsiveness; the ratio of forced expiratory flow at 40% of FVC from maximal and partial flow/volume curves (MEF40M/P) was used to assess the effect of DI on airway caliber. Thirteen patients showed a dual asthmatic response (DAR) to allergen, 5 patients an isolated early-phase asthmatic response (EAR). In the DAR patients, 3 h after allergen challenge, when the early-phase response had resolved and the late-phase response had yet to develop, MChPD20 (geometric mean) was reduced from 202 to 71 micrograms (P less than 0.001) whereas MEF40M/P at the MCh end point was unchanged (p greater than 0.4). Twenty-four hours after allergen challenge, when late-phase response had developed, MChPD20 was further reduced to 51 micrograms (p less than 0.02), and this reduction was accompanied by a decrease of MEF40M/P at the MCh end point (p less than 0.01). In the EAR patients, neither MChPD20 nor MEF40M/P was significantly changed at any time during the study. We conclude that most of the increase in airway responsiveness that follows acute exposure to allergen precedes the late-phase response and is not determined by the same mechanisms that impair the ability of the lung to dilate airways with a DI.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Dust- and endotoxin-related respiratory effects in the animal feed industry.

A cross-sectional study of 315 animal feed workers was undertaken in 14 animal feed mills in the Netherlands. Primary aims were to explore relationships between exposure to organic dust and respiratory symptoms and chronic lung function changes. The study comprised monitoring dust and endotoxin exposure, spirometric lung function measurements (FVC, FEV1, mean midexpiratory flow, and flow-volume parameters) and a questionnaire for respiratory symptoms. The exposure was measured in two periods, during spring and autumn. The average 8-h personal inspirable dust exposure was 9 mg/m3 grain dust (range, 0.2 to 150 mg/m3) and 25 ng/m3 endotoxin (range, 0.2 to 470 ng/m3) based on 530 personal dust measurements. On the basis of these measurements and the occupational history of the workers, the number of years "worked in dust" and an estimate of the cumulative dust and endotoxin exposure were calculated. The prevalence of most chronic respiratory symptoms tended to decrease with increasing years of exposure. The "healthy worker effect" is probably responsible for this finding. In general, a strong negative association between most of the exposure variables and lung function was found. The endotoxin exposure was more strongly related to decreases in lung function than the dust exposure. The estimated effects of an average (cumulative) endotoxin exposure on lung function were greater, with a higher statistical significance, than for an exposure to dust. These results suggest that endotoxin exposure is an important factor in the development of respiratory impairment. The lung function changes occur at endotoxin levels ranging from 0.2 to 470 ng/m3.

Adult↗

Effect of modification of the smoking habit on lung function.

The effect of smoking cessation or modification on lung function was determined during a 48-week period. In a large number of the cigarette smokers, a disturbance of lung function was not revealed by conventional tests, such as the 1-sec forced expiratory volume; however, an abnormality was often demonstrable in tests that may reflect alterations in small airways, such as closing volume and Phase III of the single-breath expired N2 curve. There was no relation between the degree of abnormality of lung function and the presence of respiratory symptoms, but there appeared to be a relationship to lifetime smoking history, the heaviest smokers having the poorest function. Cessation, or more than 25 per cent decrease in the number of cigarettes smoked, was attened by improvement in the slope of Phase III of the N2 washout curve, closing volume, and closing capacity, as well as forced vital capacity, 1-sec forced expiratory volume, and peak flow. Resumption of smoking after cessation was attended by a deterioration in the slope of Phase III and closing capacity. The data suggest that the functional abnormalities in smokers are related to smoking and are at least partially reversible by cessation or significant modification of the smoking habit.

Adolescent↗

Follow-up evaluation of a prevalence study for chronic bronchitis and chronic airway obstruction.

Follow-up of the prevalence study of respiratory symptoms and chronic airway obstruction was performed after a 6- to 7-year interval. One hundred fifteen of 117 subjects (98%) originally labeled "abnormal" (chronic bronchitis or asthma by history, or ratio of 1-sec forced expiratory volume to forced vital capacity less than 60 per cent), and 111 of a random sample of 116 subjects (96%) originally labeled "normal" were traced. Nineteen patients were dead, 14 "abnormal" subjects, and 5 "normal" subjects (P less than 0.01). Eighty-eight of the originally labeled "abnormal" subjects and 91 of the random "normal" sample could be retested by spirometry. Subjects with lower initial ratios of 1-sec forced expiratory volume to forced vital capacity tended to lose more 1-sec forced expiratory volume and forced vital capacity. Early identification of respiratory symptoms and spirometric abnormalities may identify persons at increased risk of death who could benefit from appropriate therapy.

Adult↗