The nose as a target for adverse effects from the environment: applying advances in nasal physiologic measurements and mechanisms.
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Publications and source records attributed to T J Witek.
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Exposure to aerosols of organic dusts such as coffee, tea, spices, soy, fur, and animal food in an occupational setting can affect the respiratory health of industrial workers. Based on our experience with workers from many small industries processing organic materials, we discuss the clinical features and possible mechanisms responsible for the respiratory impairment associated with these types of dust exposure. Significantly higher prevalences for most chronic respiratory symptoms were found among exposed workers than among control workers. Smoking appears to aggravate these symptoms. A large number of exposed workers complained of acute symptoms which developed during the work shift. In exposed workers, significant across-shift reductions in lung function were recorded for all spirometric tests, but particularly for the flow rates at 50% and 25% of vital capacity on maximum expiratory flow-volume curves. Comparison of preshift measured ventilatory capacity tests with predicted normal values indicates that these workers demonstrate obstructive changes affecting primarily flow rate at low lung volumes. The data suggest that exposure to organic aerosols in industrial settings, particularly in conjunction with smoking, may be associated with the development of chronic obstructive lung disease.
Partial expiratory flow-volume (PEFV) curves are a useful tool in airway challenge studies, but unlike the maximal expiratory flow-volume (MEFV) curve, lung function parameters require manual calculation from the flow-volume tracing. We describe an algorithm written in QuickBASIC that analyzes a PEFV curve superimposed on a MEFV curve by (1) identifying the PEFV curve, (2) locating the maximal expiratory flow at the point on the PEFV curve that corresponds to 60% of the baseline forced vital capacity (FVC) below total lung capacity (TLC), termed MEF40%(P), and (3) identifying the size of the PEFV curve along the TLC axis. A report of these parameters is also provided. This algorithm was validated using flow-volume curves from a clinical study in which eight subjects performed two sets of MEFV and PEFV curves separated by approximately 1 hr. Paired comparison of MEF40%(P) determined by the algorithm and two independent manual calculations correlated strongly and yielded no statistically significant differences between the two methods. We conclude that this algorithm provides rapid and accurate determinations of PEFV parameters.
A group of 35 men employed in the processing of animal food was studied to assess the relation between respiratory findings and immunological status. The most frequent positive skin prick reactions to occupational allergens were to fish flour (82.9%), followed by carotene (77.1%), corn (65.7%), four-leaf clover (62.9%), sunflower (54.3%), chicken meat (31.4%), soy (28.6%), and yeast (22.7%). Increased total IgE serum levels were found in 14/35 (40.0%) animal food workers compared to 1/39 (2.6%) in a healthy population (p less than 0.01). A significantly higher prevalence of chronic respiratory symptoms was found among the exposed workers compared to control workers. There was however, no significant difference in the prevalence of chronic respiratory symptoms between animal food workers with positive and negative skin tests to house dust or to fish flour or among those with increased or normal IgE (except for dyspnea). The frequency of acute symptoms associated with the work shift was high among the animal food workers but similar by immunological status. There were significant mean across-shift reductions for all ventilatory capacity tests, being particularly pronounced for FEF25. Workers with positive skin tests to fish flour antigen had significantly larger across-shift reductions in FEF25 than workers with negative skin reactions. An aqueous extract of animal food dust caused a dose-related contractile response of isolated guinea pig tracheal muscle in vitro. Our data suggest that, in addition to any immunological response animal food dust may produce in vivo, it probably also causes direct irritant or pharmacological reactions on the airways as suggested by our in vitro data.
Immunological parameters were studied in a group of 24 cotton textile workers. These were volunteers from a cohort of 106 (83 women and 23 men) previously studied textile workers. A group of 30 employees from a bottle packing plant served as a control for the immunologic studies. The subgroup of volunteers undergoing immunologic testing did not differ from the original cohort of textile workers in age, sex, smoking history, or prevalence of most chronic respiratory symptoms, nor were there any significant differences in baseline lung function or across-shift changes. The 24 cotton worker volunteers underwent skin testing with extracts of cotton dust and cotton seed. Eight of these 24 (33.3%) had positive tests, and 5 of the 8 had elevated serum immunoglobulin E (IgE) levels. Only one of the 8 skin-test-positive workers had symptoms of byssinosis. Only 1 of 30 control workers' skin tested with cotton extract reacted, and none had an increased serum IgE level (P less than 0.01). Both baseline lung function and across-shift changes did not differ between workers with positive and negative skin test reactions or between workers with normal and elevated IgE levels. Additionally, we studied the response in vitro of nonsensitized guinea pig trachea to cotton bract extract and demonstrated a dose-dependent contractile response. These data suggest that while immunological findings are frequent in textile workers, they correlate poorly with respiratory symptoms and function and may not be the basis for the airway obstruction seen in this disease.
Phenindamine, an H1-receptor antagonist that was developed almost 50 years ago, has been associated with both drowsiness and insomnia. Since its central nervous system profile has not been well characterized, we used a series of psychomotor tests to conduct two studies. In the first, 12 subjects received single oral doses of phenindamine (25 mg), diphenhydramine (50 mg), terfenadine (60 mg), or placebo in a four-way crossover study. Psychomotor tests included choice reaction time (CRT), tracking, and hand steadiness (HS). In the second trial, 15 subjects received single oral doses of phenindamine (25 mg), pseudoephedrine (60 mg), phenindamine and pseudoephedrine, diphenhydramine (50 mg), or placebo in a five-way crossover study. Psychomotor tests included CRT, HS, and a task that divided attention between tracking and reaction time. Introspective drowsiness was measured in both trials with use of a visual analog scale (VAS) and the Stanford Sleepiness Scale (SSS). All assessments were made before and 1, 3, and 5 hours after drug administration. In the first trial, diphenhydramine produced significant impairment relative to placebo (p < 0.05) in CRT, tracking, and HS tasks and higher SSS and VAS scores, with peak effect noted at 3 hours. Phenindamine did not significantly differ from placebo or terfenadine. In the second trial, diphenhydramine produced significant impairment relative to placebo (p < 0.05) in CRT, divided attention, HS, and VAS, and SSS, also peaking at 3 hours. Stanford Sleepiness Scale scores after phenindamine were greater than placebo at 3 hours (p < 0.05) but significantly less than diphenhydramine (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Immunological status and its relation to respiratory findings were studied in 42 female textile workers occupationally exposed to hemp dust and in 49 female control workers. Skin prick tests with hemp or flax dust extracts from different parts of the mill in hemp workers demonstrated the following frequencies of positive tests to antigens: a mixture of hemp and flax extracts (64%), followed by flax extracts (48%), hemp from combing machines (41%), hemp from carding machines (38%), hemp from spinning and weaving machines (33%), and hemp from softening machines (20%). The prevalence of positive skin tests to hemp or flax allergens in control workers was consistently lower, ranging from 21 to 5%. Increased total serum IgE was recorded in 35.7% of hemp workers compared to only 5.0% of control workers (P < 0.05). Hemp workers with positive skin tests had significantly higher prevalences of chronic respiratory symptoms than those with negative skin tests. There were, however, no differences for acute symptoms between workers with positive and negative skin tests. Across-shift changes and baseline lung function were not different when compared by immunologic status. We showed additionally that a water-soluble extract of hemp dust causes a dose-related contraction of nonsensitized guinea pig tracheal smooth muscle when studied in vitro. Our results suggest that frequent immunologic abnormalities can be documented in hemp workers but, with the exception of chronic respiratory symptoms, in general, these do not correlate with respiratory findings.
The effects of CAAD (diphenhydramine hydrochloride, 50 mg; pseudoephedrine hydrochloride, 60 mg; acetaminophen, 1 g in 10% ethanol) were evaluated in a double-blind, three-way, placebo-controlled, cross-over study on 18 volunteers with allergic rhinitis. The number of sneezes following nasal challenge with antigen was significantly reduced after a bed-time dose of CAAD (P less than .005) and a single dose of diphenhydramine (P less than .001) given 2 hours before the challenge. The levels of N-alpha-tosyl-L-arginine methyl ester (TAME) activity decreased after diphenhydramine treatment, while histamine levels following challenge were not different. The drowsiness reported after CAAD was equal to placebo, but significantly less than diphenhydramine (P less than .002 for both). The active treatments reduced the actions of histamine without suppressing its release from mast cells. The effect of CAAD persists 10 hours after administration without inducing drowsiness.
The objective of this study was to evaluate the effect of 60 micrograms oxymetazoline on nasal mucosal blood flow (NMBF) measured by laser Doppler velocimetry. Nasal airflow (measured by anterior rhinomanometry) and subjectively perceived airflow (measured by visual analog scales) were also evaluated. A reduction of NMBF (mL/100 g tissue/min) was observed following local application of 60 micrograms oxymetazoline that was not observed after the vehicle was applied. For example, NMBF at baseline was measured at 78.8 +/- 10.3 mL/100 g tissue/min (mean +/- SEM). During the five minutes following vehicle application, mean values remained at 81.8 +/- 8.8 mL/100 g tissue/min. Five minutes after topical oxymetazoline treatment, NMBF was reduced 49% to 38.3 +/- 10.2 mL/100 g tissue/min. Nasal airflow (mL/sec), which was measured before and after LDV probe placement, was not significantly increased in either the ipsilateral (281.4 +/- 33.1 to 314.3 +/- 31.6) or contralateral nostril (335.7 +/- 26.9 to 262.1 +/- 36.4), probably due to the limited surface application of drug. Subjective assessments of congestion by both the investigator and the subject showed significant improvements in the ipsilateral nostril. We conclude that, under the conditions of our study, localized application of 60 micrograms oxymetazoline significantly reduces superficial nasal blood flow and provides subjectively perceived improvements in nasal stuffiness.
Immunological and respiratory findings were studied in a group of 19 male soybean workers. Twenty control workers also participated in the immunological studies. All soybean workers had positive immediate skin reactions to soybean extract, as did 19/20 control workers. Similarly, 18/19 soy workers reacted to soy antigen prepared after separation from oil, but only 3/19 to soy lecithin antigen and 1 to soy oil antigen. A majority of soy workers (13/19) reacted to house dust. Only 3/19 soy workers had increased levels of soy-specific IgE. The prevalence of chronic respiratory symptoms was higher in exposed than in control workers, being significantly different for dyspnea (P less than 0.01). Workers with increased specific serum IgE or positive skin tests to house dust did not have any more symptoms than workers with negative tests. Ventilatory function was significantly worse in soybean workers than expected. Nevertheless, workers with positive skin or serological tests to house dust had across-shift changes similar to those with negative tests. These data suggest that skin and airway responses to soybean components (particularly the non-lipid ones) are very frequent among soybean workers. In the current study specific (soy) and non-specific (house dust) skin tests and immunoglobulins did not allow us to identify the workers at risk of developing symptoms or lung function abnormalities. This suggests that in addition to any atopic mechanisms, the irritant effect of soy dust may play a role in this occupational airway disease.
A follow-up study of respiratory function in cotton textile workers was performed 10 yr after the original cross-sectional study (1975 to 1985). There were 35 nonsmoking female and 31 smoking male textile workers restudied from the original group of 116. The majority of those lost to follow-up had left the industry. The prevalence of byssinosis among the female workers at the time of follow-up was 15/35 (42.9%) compared with 8/35 (22.9%) at the time of the initial study (p = 0.063). For men the byssinosis prevalence at follow-up was 16/31 (51.6%) compared with 8/31 (22.9%) at the time of the initial study (p = 0.03). Similarly, the prevalence of almost all other respiratory symptoms was significantly higher at the follow-up than at the time of the initial study. Significant across-shift decrements in FEV1 and FVC were documented at both surveys. The mean annual decline in ventilatory capacity was greater than expected for both female (FVC: -0.036 +/- 0.005 L/yr; FEV1: -0.059 +/- 0.009 L/yr) and male workers (FVC: -0.059 +/- 0.008 L/yr; FEV1: -0.068 +/- 0.006 L/yr) (Mean +/- SE). The mean total airborne dust concentration measured at the time of the follow-up study was 3.95 mg/m3 with an average respirable dust concentration of 0.97 mg/m3. We conclude that continued exposure to high dust concentrations in the cotton textile industry is associated with an increasing prevalence of respiratory symptoms and progressive impairment of lung function. The increase in respiratory impairment was seen both in smokers and nonsmokers.
The lung function response to inhalation of an extract of green coffee was studied in ten healthy subjects who were prescreened for airway hyperresponsiveness to an aerosol of green coffee extract. The effects of this provocation were evaluated at rest and following moderate exercise as well as with and without pretreatment with 80 mg of disodium cromoglycate (DSCG). There was a statistically significant decrement in lung function over time (P less than .001) following coffee provocation both at rest and following exercise. No significant protection against this response was observed with DSCG pretreatment. While the majority of these "healthy" coffee reactors exhibited baseline nonspecific airway hyperresponsiveness to methacholine (PC20 FEV1 less than 25 mg/mL in 7/10), there was no correlation in these ten subjects between baseline responsiveness to methacholine and the degree of lung function decrement following coffee (P greater than .05). Also, no correlation was observed between skin prick and lung function response to coffee extract. We conclude that inhalation of green coffee extract causes significant bronchoconstriction in selected healthy volunteers and that this response is not prevented by pretreatment with DSCG.
Respiratory symptoms and abnormalities of lung function were studied in 84 female and 27 male hemp workers employed in two textile mills (A and B) processing soft hemp (C sativa). In mill A 46 women and 27 men were investigated and 38 female workers were studied in mill B. Forty nine women and 30 men from a non-dusty industry served as controls. A significantly higher prevalence of almost all chronic respiratory symptoms was found in female hemp workers when compared to control workers. Among the men these differences were significant for nasal catarrh and sinusitis. A high prevalence of byssinosis was found among female hemp workers in both mills (group A, 47.8%; group B, 57.9%) as well as in the male workers (66.7%). Statistically significant across shift reductions in lung function were found for all ventilatory capacity measurements in female and male hemp workers varying from 7.1% for forced expiratory volume in one second (FEV1) to 15.1% for flow rates at 50% vital capacity (FEF50). Measured Monday baseline values before the work shift were significantly lower than expected for hemp workers, being particularly reduced for FEF25 and FEF50. The data suggest that occupational exposure to hemp dust is a significant risk factor for the development of acute and chronic lung disease in workers employed in this textile industry.
A group of 71 men employed in animal food processing was studied to assess the prevalence of acute and chronic respiratory symptoms and the presence of lung function abnormalities. In addition, a control group of 55 unexposed men was studied for the prevalence of chronic respiratory symptoms. A significantly higher prevalence for most of the chronic respiratory symptoms was found among the exposed workers compared to the control workers. Those workers who smoked had a significantly higher prevalence of chronic cough, chronic phlegm, chronic bronchitis, and chest tightness than the smokers in the control group. For nonsmokers, the differences between exposed and control workers were significant for chronic phlegm and chest tightness. The frequency of acute symptoms associated with the work shift was high among the animal food workers. There were significantly lower measured values for FVC, FEV1, and FEF50 in the exposed group (smokers and nonsmokers) compared to predicted lung function values. In smokers, all measured parameters of ventilatory capacity were significantly less than predicted; for nonsmokers, the FVC and FEV1 were less than normal. Our data indicate that exposure to dust in the animal food industry may be associated with the development of acute and chronic respiratory symptoms and the impairment of lung function. Smoking, in this setting, appears to aggravate these changes.
Cotton textile workers have an increased prevalence of both obstructive and restrictive lung function patterns compared with control subjects. Similar abnormal patterns may occur with respiratory diseases of other etiologies, notably those associated with cigarette smoking. The shape of the maximum expiratory flow volume (MEFV) curve has been used to characterize patterns of lung function abnormality. To better evaluate the respiratory effects of cotton dust exposure and to contrast them with those of cigarette smoking, we defined a new functional parameter (angle beta) related to the shape of the MEFV curve. We compared 477 cotton textile workers, both current smokers and never smokers, 45 years and older, with 932 similarly aged control subjects from three communities. Smokers, regardless of their occupational exposure or sex, have smaller beta values than nonsmokers. Cotton textile workers, despite a greater prevalence of abnormal lung function, have beta values that do not differ from those of persons without occupational exposure to cotton dust. We suggest that morphologic patterns of flow volume curves reflect separate effects of cotton dust exposure and smoking and may be related to different sites of airway injury.
The acute effect of herbal tea dust extracts on lung function was studied in 15 of 25 healthy subjects responding to the inhalation of these extracts. Bronchial inhalation challenge was performed with tea extracts (sage, dog rose and gruzyan) and with normal saline solution as a control substance to assess their baseline airway reactivity to an isotonic aerosol. Lung function testing was performed before exposure and at 0, 15, 30, and 60 minutes after the cessation of exposure. The same subjects were also tested by challenge with methacholine. Lung function was measured by recording FVC, FEV1, FEF50, FEF25, SGaw, and Raw. Subjects were skin tested by the skin prick method and serum IgE levels were determined. The findings suggested that neither baseline nonspecific airway reactivity nor specific markers of immediate sensitivity to tea predict airway responses to tea extracts. Further evaluation of immunologic markers may help to explain the onset and progression of airway disease in workers.
Respiratory function was studied in a group of 29 soy workers exposed to soy bean dust produced after extraction of soy oil. The prevalence of all chronic respiratory symptoms was consistently higher in exposed than in control workers, although the differences were not statistically significant. During the Monday work shift there was a significant mean acute across-shift decrease in maximum expiratory flow rates at 50% and 25% vital capacity (FEF50: -6.4%; FEF25: -12.4%). Changes in vital capacity (FVC: -3.6%) and 1-sec forced expiratory volume (FEV1: -2.7%) were smaller, but still statistically significant. There were also statistically significant acute reductions in all ventilatory capacity parameters over the work shift on the following Friday, although the changes were in general smaller than on Monday (except for FEV1). An analysis of Monday preshift values of ventilatory capacity in soy bean workers suggests that exposure to soy bean dust may lead to chronic respiratory impairment in some workers.
It is well established that cotton dust inhalation can compromise lung function in textile workers. Challenges with a water-soluble extract of cotton bract (CBE) can also induce reversible airway obstruction in healthy volunteers. We have examined the effect of inhaled CBE in nonhuman primates and have attempted to inhibit the bronchoconstrictive response with mediator modifying compounds. CBE (34 mg/ml or 100 mg/ml) was administered via IPPB for 15 minutes (15 breaths/min) in 12 intubated, anesthetized, adult male monkeys (Macaca fascicularis). Breath-by-breath determinations of pulmonary resistance, dynamic compliance (Cdyn), tidal volume, and breathing frequency were calculated from the transpulmonary pressure (esophageal balloon) and airflow signals and monitored for 2 hr postchallenge. Control challenges with distilled water were also performed in 3 monkeys with the greatest response from CBE. Five animals (42%) were found to respond to CBE with peak % changes in Cdyn greater than 45%. In 3 of these animals, we attempted to blunt the CBE response with chlorpheniramine (0.1 mg/kg i.v.) and a mast cell stabilizer lodoxamide (0.1 mg/ml aerosol). In these 3 animals the mean (+/- SD) peak % changes in Cdyn to CBE alone was -47.4 +/- 1.8. The CBE response following chlorpheneramine was -49 +/- 15.7 and following lodoxamide was -47.0 +/- 5.4. These data suggest that monkeys, like humans, can develop reproducible bronchoconstriction following an aerosol challenge with CBE. Furthermore, this bronchoconstriction in the monkey is probably not explained by the action of histamine or mediator release alone and an acute inflammatory reaction may be involved.