Sera from 99 subjects exposed to the industrial gas leak in Bhopal on December 2, 1984 were studied along with sera from guinea pigs exposed to methyl isocyanate (MIC) to determine the production of antibodies specific to (MIC). Each of the four guinea pigs injected with the reactive isocyanate produced MIC-specific antibodies in titres of 1:5120 to 1:10240, when tested with MIC-guinea pig albumin antigen conjugate. Analogous antigens prepared by reaction of MIC with human serum albumin were used to probe production of antibodies in 264 serially obtained human sera from 99 subjects from Bhopal. MIC-specific antibodies belonging to IgG, IgM and IgE classes were detected in eleven subjects. Though titres were low and transient (declining after several months) these findings indicate that the single large exposure to MIC resulted in an immunologic response. This finding was concomitant with chronic respiratory effects following MIC exposure.
A change from the supine to upright posture in anesthetized dogs promotes increased expiratory muscle use during breathing. To examine the role of cardiovascular receptors in eliciting this expiratory muscle recruitment, the electromyographic (EMG) activity of the triangularis sterni (TS) and abdominal external oblique (EO) muscles was recorded in seven spontaneously breathing animals during head up tilting and during occlusion of the inferior vena cava. Head up tilting was associated with a reduction in cardiac output, a transient fall in systemic blood pressure, and considerable increases in TS and EO expiratory EMG activity. On an average (mean ± SE), the amount of TS and EO expiratory activity in the supine posture was 44.7 ± 12.9 and 10.3 ± 7.3%, respectively, of the activity recorded in the 80° head up posture. When occlusion of the inferior vena cava in the supine animals induced a reduction in cardiac output and a fall in systemic blood pressure that were comparable to those measured during head up tilting, the TS and EO expiratory EMG activity also increased. This activity, however, always remained smaller than that recorded during breathing in the upright posture; for the seven animals, the amount of TS and EO expiratory activity during vena cava occlusion was only 58.4 ± 5.7 and 17.9 ± 10.4% of the activity in upright posture, respectively (P < 0.001 for both muscles). We conclude, therefore, that the reduced venous return and systemic hypotension of the upright posture are not the critical sensory events for promoting the increased expiratory muscle use in this posture. It must, therefore, be elicited by respiratory receptors.
Two healthy subjects performed single breath tests, the inspired gas containing 90% O2, 5% He and 5% SF6. The slope of the alveolar plateau was computed for N2, HE and SF6. The following experimental conditions were considered variable: (1) preinspiratory lung volume (PILV) with inspired volume (VT) equal to 1 L, (2) VT with PILV equal to functional residual capacity (FRC) with and without 10 sec of breath-hold (BH) time, (3) VT with PILV = FRC + 1 L, (4) flow with VT = 1 L and PILV = FRC with and without 10 sec end inspiration BH and (5) BH time with VT = 1 L and PILV = FRC. The slope dependence on the different variables was compared with simulations performed with two multibranch point models of the human acinus with different asymmetries. The model simulations give a coherent picture of all the experimental observations. The present work gives support to previous analyses which suggest that inter-dependence of transport by convection and diffusion in the periphery of the lung is a major component of the slope of the alveolar plateau.
The need for performance control of spirometers has been studied in Helsinki hospitals. The performance of 27 instruments was measured using 11 technical test parameters. The performance was assessed by calculating figures of merit (FM) determined as a weighted sum of the test results. 55% of the devices failed the test. Performance was specific for each instrument, was dependent on maintenance but independent of instrument age. Specific attention to accuracy is recommended in measuring rapid forced expiratory parameters with wedge-type volume meters sealed with bellows. Although daily calibration is helpful, it is not sufficient to maintain optimal performance. Device maintenance should start from acceptance trials to detect manufacturing problems and be complemented by periodic technical performance tests.
We tested whether measurement of peak flow was useful in determining the presence and severity of restrictive pulmonary disorders in addition to its recognized use in the diagnosis and management of airflow obstruction. In 102 patients with various causes of restriction of lung volumes, we found that peak expiratory flow correlated well with forced vital capacity. As a diagnostic test it was useful in restrictive disorders, except in fibrosing alveolitis where it consistently failed to detect abnormality.
To investigate the mechanisms of pulmonary gas-exchange impairment in idiopathic pulmonary fibrosis (IPF) and to evaluate their potential relationship to the CO diffusing capacity (DLCO), we studied 15 patients with IPF (mean DLCO, 52% of predicted) at rest (breathing room air and pure O2) and during exercise. We measured pulmonary hemodynamics and respiratory gas-exchange variables, and we separated the ventilation-perfusion (VAQ) mismatching and O2 diffusion limitation components of arterial hypoxemia using the multiple inert gas elimination technique. At rest VA/Q mismatching was moderate (2 to 4% of cardiac output perfusing poorly or unventilated lung units), and 19% of AaPO2 was due to O2 diffusion limitation. During exercise VA/Q mismatch did not worsen but the diffusion component of arterial hypoxemia increased markedly (40% AaPO2, p less than 0.005). We observed that those patients with higher pulmonary vascular tone (more release of hypoxic pulmonary vasoconstriction) showed less pulmonary hypertension during exercise (p less than 0.05), less VA/Q mismatching [at rest (p less than 0.005) and during exercise (p less than 0.0025)], and higher arterial PO2 during exercise (p = 0.01). We also found that DLCO corrected for alveolar volume (KCO) correlated with the mechanisms of hypoxemia during exercise [VA/Q mismatching (p less than 0.025) and O2 diffusion limitation (p less than 0.05)] and with the increase in pulmonary vascular resistance elicited by exercise (p less than 0.005). In conclusion, we showed that the abnormalities of the pulmonary vasculature are key to modulate gas exchange in IPF, especially during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
The temporal and quantitative relationship between increases in airway responsiveness and late asthmatic reactions provoked by inhalation challenge with occupational agents was studied in nine individuals who underwent a total of thirteen active inhalation challenge tests with one of the following agents: toluene diisocyanate (TDI), maleic anhydride (MA), trimellitic anhydride (TMA), carmine, or colophony (pine wood resin). Airway responsiveness to inhaled histamine (histamine PC20) was measured before and at approximately 3 and 24 h after control and active challenge exposure, when, on all but four occasions, FEV1 was within 10% of pre-challenge values. Significant increases (p less than 0.02) in histamine responsiveness were present at 3 h following challenge exposures which subsequently provoked a definite late asthmatic reaction (FEV1 decrease greater than 15% 3-11 h post challenge). These increases in histamine responsiveness were significantly greater than those at 3 h following the challenges which provoked an isolated early (FEV1 decrease less than 6% 3-11 h post-challenge) or equivocal late asthmatic reaction (FEV1 decrease 6-15% 3-11 h post-challenge) (p less than 0.03). Although histamine responsiveness remained high at 24 h after challenges provoking late asthmatic reactions (p less than 0.05), this was less than the increase at 3 h and not significantly different from the PC20 at 24 h after challenges provoking either single early or equivocal late asthmatic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)
To assess the risk of byssinosis in a cotton textile factory in Cameroon a preliminary study was conducted on a random sample of 125 men from production areas and 68 men from non-production areas. Symptoms were assessed by a questionnaire, which also included questions regarding sleep; peak expiratory flow rate (PEF) was measured with a miniature peak flow meter at the end of a working day and total dust concentrations were assessed by static and personal sampling with Casella dust samplers giving values of 6.4 +/- 2.6 mg/m3 (m +/- SD) in production areas and 1.7 +/- 0.7 mg/m3 in control areas. Exposed subjects had significantly more symptoms (particularly in smokers) and lower PEF values than controls (408 +/- 961/min v 468 +/- 701/min, p less than 0.001). Twenty three exposed subjects (18%) reported chest tightness on returning to work after the weekly break (compared with one control, p less than 0.01). Subjects with byssinosis had lower PEF values than those without chest tightness (356 +/- 501/min v 426 +/- 951/min, p less than 0.01), more chronic bronchitis (52% v 6%, p less than 0.001), they were more often smokers (61% v 31%, p less than 0.05), and came generally, though not exclusively, from the opening carding spinning department with the highest concentrations of total dust (8 +/- 2 mg/m3) and an estimated prevalence of byssinosis of 28%. There were no significant differences in sleep related symptoms between the exposed and controls, though the 23 subjects with byssinosis tended to report more snoring (48%), early morning headache (48%), and sleep improvement over the working week (44%) than all the other subjects (28%, 24%, and 24% respectively, p less than 0.1).
Several studies on the prognosis of isocyanate-induced asthma show that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work, and that further exposure to isocyanates in sensitized subjects leads almost invariably to persistence of respiratory symptoms and of bronchial hyperresponsiveness and the deterioration of airway function. Specific bronchial reactivity to isocyanates may change after cessation of work; however, some subjects continue to be sensitive to TDI several months after cessation of work. The determinants of an unfavourable prognosis for asthma seem to be the same as those for other types of occupational asthma due to low molecular weight compounds (i.e. red cedar asthma): long duration of exposure before the onset of asthma, long duration of symptoms before diagnosis, airway obstruction, and dual airway response after specific challenge tests. Also, single acute exposure to high levels of TDI in the workplace (spills) can result in persistent nonspecific bronchial hyperresponsiveness. Potential mechanisms of persistence of symptoms and of nonspecific bronchial hyperresponsiveness may be chronic inflammation, bronchial smooth muscle alteration, autonomic nervous system disregulation.
The experiments were performed with thirteen anaesthetized rabbits breathing spontaneously through the larynx. Phrenic output was measured during tidal respiration in control conditions and in the course of progressive denervation of the laryngeal and tracheobronchial compartments. We have analysed changes in amplitude and the rate of rise of the integrated phrenic neurogram as well as the changes in TI, TE, TT and f of the respiratory timing after superior laryngeal nerves (SLN-s) section, section of the recurrent laryngeal nerves (RLN-s) and step-wise complete midcervical vagotomy. Nerve sections were performed by two methods: 1) bilateral SLN-s, RLN-s and cervical vagal neurotomy (horizontal method); 2) right-sided neurotomies of SLN, RLN and vagus followed by left-sided neurotomies of these nerves (vertical method). Laryngeal deafferentation did not greatly affect respiratory variables. Unilateral and especially bilateral vocal cord paralysis prolonged the respiratory cycle with enhanced TI/TT ratio, increased amplitude and rate of rise of the integrated phrenic neurogram. Maximum values of all parameters (the rate of rise excluded) were achieved after complete midcervical vagotomy. Of the two methods of denervation, the right-sided followed by left-sided denervation led to better adaptation of the organism to the respiratory disturbance (smaller changes in TI and TE compared with the control values). Denervation by the 'horizontal' method (paired section of the nerves) led to an abrupt failure of effective ventilation.
We have investigated the morphological effects of an intratracheal challenge with 50 micrograms ovalbumin (OA) on sensitized rat tracheas, in vivo. Female Sprague-Dawley rats were primed ten days before challenge with a single i.t. injection of 100 micrograms OA plus Bordetella pertussis (OA-BP). Two additional groups of animals served as controls: primed animals challenged with saline only and non-primed but OA-challenged animals. Sacrifices--and subsequent morphological studies--were performed prior to and 5, 15 and 60 min after challenge. At each time, the total numbers of epithelial nuclei, subepithelial mast cells (SEMC) and intraepithelial mast cells (IEMC) were scored in six non-adjacent cross sections per trachea. We found that: 1) priming with OA-BP alone did not induce any change in the tracheal mucosa with respect to morphological structure and mast cell counts; 2) no morphological change nor significant modification of the cell counts occurred at any time in tracheas from either of the control groups; 3) in contrast, a luminal heterogeneous exudate and a subepithelial oedema developed in 9 of the 15 tracheas of primed animals within 60 min of OA challenge. In those nine tracheas, the scores of intraepithelial nuclei, of IEMC and of SEMC were found to decrease significantly 15 min after challenge as compared with starting values (p less than 0.05 for each score). The decrease in the number of mucosal mast cells is probably related to the damages of the epithelial cells and to the difficulty with which depleted mast cells can be seen by toluidine blue staining.
We studied the acute effect of a single, oral dose of 200 mg almitrine and of placebo on arterial blood gas tensions, ventilation, gas exchange and pulmonary mechanics in 28 patients with chronic obstructive bronchitis and emphysema (COPD), 20 patients with bronchial asthma and 10 patients with interstitial lung disease. Almitrine significantly increased PaO2 in COPD, had a borderline effect in bronchial asthma and no effect in lung fibrosis. In all groups of patients almitrine significantly increased minute ventilation and decreased arterial carbon dioxide tension (PaCO2). Placebo had no effect on arterial oxygen tension (PaO2) and PaCO2 in any of the groups. Therefore, despite similar effects on ventilation, the improvement of arterial PO2 by almitrine depends on the underlying disease.
