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Medical evidence hints that asymptomatic recruits with a history of childhood asthma, quiescent since their 13th birthday, are still at risk for adverse changes in their clinical status following unfavorable environmental exposures during military deployment or combat. Asthmatic persons, claiming none or few symptoms, may still manifest airflow obstruction and display biomarkers of airway inflammation even when they are relatively asymptomatic and experience few if any respiratory complaints. The occupational medicine model offers a credible foundation for acknowledging the importance of personal susceptibility in the pathogenesis of military-associated asthma. It is appropriate to re-explore the current military standard for recruits with asymptomatic childhood asthma (≥12 months) not prescribed antiasthma medications. Raising the acceptance age for these recruits may be a consideration. Unfortunately, there is no effectual screening test that recognizes such susceptible soldiers at risk for future asthma attacks. Nevertheless, there is general support for evidence-based, scientifically valid medical screening that judges fitness for military service. Screening tests comprising asthma biomarkers and genetic indices may better verify vulnerable soldiers destined to suffer future asthma reactivation.

Preview Patients affected by occupational asthma have respiratory symptoms that may persist for months, years, or even life. Hundreds of substances have been implicated in the disease, and the list is expected to grow. The authors discuss management of this sometimes life-threatening condition and emphasize the importance of environmental controls to prevent future cases.

The manuscript embodies case material and the author’s extensive personal experience to address a perceived or actual airborne exposure when incorrectly judged as due to intrathoracic/lung damage when in reality the outcome is the more innocuous extrathoracic/upper airway’s vocal cord dysfunction (VCD). Because of the conviction of possible lung injury, the individual applies the fetal protective glottic closure reflex to counteract an odorant cue instigating acute VCD. Breathing against an obstructed glottis as well as hyperventilation from anxiety, panic and/or fear of personal harm worsens the laryngeal spasm. Spirometer shows flattening of the inspiratory loop of the flow-volume curve and endoscopy, while not done, would reveal adduction of the anterior two-thirds of the vocal cords with posterior chinking creating a diamond shape configuration. Successful therapy and management of VCD requires a speech therapy approach rather than physician prescribed medications.

Introduction: There are inconsistencies as to the effects of age on the human cough reflex. The investigation speaks to the Federal Drug Agency’s (FDA) trepidations for conducting inhalation experiments with non-approved medications/chemicals. The investigation addresses the accuracy of the mixing methodology and analysis of capsaicin stability during seven months of storage. Methods: There is stringent safety monitoring while conducting 12 serial (0.49-1000 uMol) single breath capsaicin inhalation challenge testing (CICT) on 20 younger and 20 older healthy research volunteers using pharmaceutical-grade capsaicin (i.e., Investigational New Drug protocol-IND 69,642). The research design and subject safety measures are recommended by the Food & Drug Agency (FDA) and approved by the Institutional Review Board (IRB). Mixing of inhaled capsaicin solutions are by a Registered Pharmacist and concentration verifications are by high performance liquid chromatography (HPLC). Potency of stored capsaicin (i.e., refrigerated and shielded from UV light) is examined over 7 months. Results: There are neither adverse reactions nor statistically significant difference in capsaicin cough parameters for older and younger volunteers at any dose of capsaicin. Physiologic monitoring by spirometry, impulse oscillometry, exhaled breath nitric oxide, electrocardiography, blood pressure, pulse and oxygen saturation measurements do not change at any dose. There are differences between the concentrations of capsaicin solutions mixed by a Registered Pharmacist and actual capsaicin determination by HPLC. The differences in capsaicin concentrations are 28.1% lower for 0.49 uMol compared to a 2.2% lesser concentration for 1000 uMol solution. During storage, capsaicin remains stable for 3-months but substantially falls by six (p

Thousands of persons experience accidental high-level irritant exposures each year but most recover and few die. Irritants function differently than allergens because their actions proceed nonspecifically and by nonimmunologic mechanisms. For some individuals, the consequence of a single massive exposure to an irritant, gas, vapor or fume is persistent airway hyperresponsiveness and the clinical picture of asthma, referred to as reactive airways dysfunction syndrome (RADS). Repeated irritant exposures may lead to chronic cough and continual airway hyperresponsiveness. Cases of asthma attributed to repeated irritant-exposures may be the result of genetic and/or host factors.

Occupational and environmental irritants play a role in the pathogenesis of chronic cough. An irritant is a non-corrosive chemical, which causes a reversible inflammatory change on living tissue by chemical action at the site of contact. The clinical and pathologic spectrum of chemically induced respiratory tract irritation ranges from neurogenically mediated alterations in regional blood flow, mucus secretion, and airway caliber to the initiation of cough. In an evolutionary perspective, two types of cough reflexes were created for different protective purposes, but each type used the same anatomic and physiologic neural and muscular structures. The mechanosensory type evolved as human ancestors adapted phonation over olfaction and the larynx moved in close proximity to the esophageal opening. The chemosensory type evolved to protect against an injured lung from a respiratory tract infection or after inhaling high levels of irritant gases and particulates that accumulated in confined quarters of early times. For this latter type of cough reflex, normally quiescent transient receptor potential (TRP) cation channels TRPV1(vanilloid) and TRPA1 (ankyrin) become activated or hyperactivated after lung injury, with lung inflammation, or in response to chemicals. Although animal and laboratory investigations support the possibility of human TRPpathies, further investigations are essential for the further elucidation of the role of TRP cationic channels in instigating chronic cough in humans.

Background A previous American College of Chest Physicians Consensus Statement on asthma in the workplace was published in 1995. The current Consensus Statement updates the previous one based on additional research that has been published since then, including findings relevant to preventive measures and work-exacerbated asthma (WEA). Methods A panel of experts, including allergists, pulmonologists, and occupational medicine physicians, was convened to develop this Consensus Document on the diagnosis and management of work-related asthma (WRA), based in part on a systematic review, that was performed by the University of Alberta/Capital Health Evidence-Based Practice and was supplemented by additional published studies to 2007. Results The Consensus Document defined WRA to include occupational asthma (ie, asthma induced by sensitizer or irritant work exposures) and WEA (ie, preexisting or concurrent asthma worsened by work factors). The Consensus Document focuses on the diagnosis and management of WRA (including diagnostic tests, and work and compensation issues), as well as preventive measures. WRA should be considered in all individuals with new-onset or worsening asthma, and a careful occupational history should be obtained. Diagnostic tests such as serial peak flow recordings, methacholine challenge tests, immunologic tests, and specific inhalation challenge tests (if available), can increase diagnostic certainty. Since the prognosis is better with early diagnosis and appropriate intervention, effective preventive measures for other workers with exposure should be addressed. Conclusions The substantial prevalence of WRA supports consideration of the diagnosis in all who present with new-onset or worsening asthma, followed by appropriate investigations and intervention including consideration of other exposed workers.

This article expands the author's presentation at the First American Cough Conference in New York City, June 8-9, 2007. The results of a scientific literature search and application of personal research findings are included. A new hypothesis to explain irritant-induced cough as a being a dysfunction of the transient receptor potential vanilloid 1 (TRPV1) cation channels located in pulmonary excitable cells is presented. The TRPV1 cation channels regulate cellular transmembrane voltage by raising intracellular Ca(2+) and Na(+) concentrations and depolarizing sensory nerve cells containing C-fibers. The discussion centers on the "capsaicin receptor" (TRPV1) and another important ion channel, TRPA1. The author reviews results of published scientific investigations to support his contention that neural events, initiated by TRPV1 ion channels, lead to a cascade of alterations that progress to a cough endpoint. A potential mechanism to explain chronic cough in conditions where there is repeated or severe irritant-induced airway epithelial injury (e.g., RADS) is through persistent TRPV1 channel activation (e.g., TRPV1pathy) with accumulation of inflammatory mediators, tachykinins, and the release of neurotrophins leading to persistent cough and airway inflammation. The significance of the hypothesis is that, if proven, it may provide new therapeutic approaches for the treatment of chronic cough.

Measurement of airway pH has been used as a diagnostic and monitoring tool in a variety of pulmonary diseases in adults. These diseases occur across a wide age range. Few investigations have addressed the effects of aging on airway pH and ammonia. The aim of this study was to determine whether exhaled breath condensate (EBC) measurements of pH and ammonia differ in older and younger populations of normal subjects. Twenty-three normal younger individuals (median age-24 years) and 25 normal older participants (median age-72 years) were investigated by measuring EBC for pH and ammonia using recommended methodologies. EBC ammonia and pH values were not significantly different between younger and older individuals. Thus, we conclude that EBC ammonia and pH do not appear to be affected by age.

The second Jack Pepys Workshop on Occupational Asthma was held in Toronto, Canada, in May 2004. The present report summarises key questions and research needs as identified by the international participants. The audiotapes from the workshop discussions were summarised by the organising chairs of the Symposium and the resulting document was circulated for input from all invited workshop participants. In total, 100 key questions and research needs were identified. Identified needs included: provision of different definitions depending on the use of data; explanations for differences in frequency studies; and better characterisation of genetic and environmental determinants of occupational asthma. The role of irritants and the pathogenesis of various forms of work-related asthma need further research, and there are also questions and research needs for diagnosis, prevention and understanding of persistence and airway remodelling. In conclusion, although advances have been made in the understanding of occupational asthma and other work-related asthma, further key issues remain that need addressing.

Introduction The specific causes and mechanism(s) for asthma occurring among occupants of nonresidential buildings with poor indoor air quality are not known, but allergic and nonallergic processes are possible explanations Methods Repeated indoor air quality measurements were made while employees were working in a building where cigarette smoking was allowed. Seven of 19 employees who sought medical care from their private physicians because of respiratory complaints received a diagnosis of asthma. Subsequently, 19 symptomatic employees were examined at the University of South Florida (USF) 2 ± 0.8 months (mean ± SD) after removal from the building. Results The first floor of the building, where employee complaints were prevalent, was characterized by markedly reduced outdoor fresh air supply, diminished air circulation to the occupant spaces, and elevated airborne concentrations of formaldehyde. Nineteen workers examined at the USF 2 ± 0.8 months after leaving the building reported ear, nose, and throat irritation and asthma-like symptoms while working in the building. There was resolution of symptoms in most of the seven employees (37%) with asthma previously diagnosed by their private physician. In fact, 16 of 19 subjects (84%) reported resolution or significant improvement of symptoms. Among 11 persons with symptoms suggesting asthma while working in the building, 4 persons (21%) showed a negative provocative concentration of methacholine producing a 20% fall in FEV 1 , including two subjects with doctor-diagnosed asthma. Conclusions Confirmation of building-related asthma is influenced by time factors and the clinical criteria used for diagnosis. A nonallergic mechanism seems operative in our cases. While considered an example of occupational asthma, building-related asthma is a challenge for the practicing physician to confirm retrospectively.

The Occupational Medicine Forum is prepared by the ACOEM Occupational and Environmental Medical Practice Committee and does not necessarily represent an official ACOEM position. The Forum is intended for health professionals and is not intended to provide medical or legal advice, including illness prevention, diagnosis or treatment, or regulatory compliance. Such advice should be obtained directly from a physician and/or attorney.

The Occupational Medicine Forum is prepared by the ACOEM Occupational and Environmental Medical Practice Committee and does not necessarily represent an official ACOEM position. The Forum is intended for health professionals and is not intended to provide medical or legal advice, including illness prevention, diagnosis or treatment, or regulatory compliance. Such advice should be obtained directly from a physician and/or attorney.

Diagnosing an environmental or occupationally related pulmonary disorder often involves a process of elimination. Unlike commonly diagnosed conditions in other specialties, a cause-and-effect relationship may be implied, yet other factors such as temporality and biologic plausibility are lacking. Our patient was referred with a suspected work-related pulmonary disorder. For several years, she had suffered with dyspnea on exertion and repeated flulike illnesses. She worked at an automobile repair garage that performed a large number of emission tests, and there was concern that her workplace exposures were the cause of her symptoms. After a careful review of her history, physical examination, and laboratory testing, we came to the conclusion that she had hypersensitivity pneumonitis related to pet cockatiels in her home. Clinical points of emphasis include the importance of a complete environmental history and careful auscultation of the chest when performing the physical examination. In addition, we encountered an interesting physical diagnostic clue, a respiratory sound that assisted with the eventual diagnosis.

Irritant-induced asthma affects about one-fifth of workers with the diagnosis of 'occupational asthma'. There are believed to be two types of irritant-induced asthma. Single exposure-type of irritant-induced asthma occurs when a person inhales a very high concentration of an irritant gas, vapor or fume to manifest newly-developed asthma symptoms plus nonspecific airway hyperresponsiveness within 24-hours following the exposure. In contrast, repeated exposure irritant-induced asthma evolves when a purportedly genetically predisposed individual is repeatedly exposed to non-massive levels of an irritant gas, vapor or fume (or as a mixture) over a few days, weeks or months and eventually develops clinical asthma. The treatment of RADS is similar to the treatment afforded patients suffering from an acute inhalational injury. Aerosolized bronchodilators are essential for treating acute bronchoconstriction. Likely, oral corticosteroids are not effective. There is no human study showing efficacy of oral corticosteroids in the treatment of RADS. Inhaled steroids have been found effective in reducing airway hyperresponsiveness in a case considered to be RADS.

A retrospective investigation of 86 asthmatic subjects defined clinical features of irritant-induced asthma and assessed the contributory role of an allergic predisposition. Three categories of asthma were evaluated: (1) occupational asthma due to a sensitizer (11 subjects, 13%); (2) irritant-induced asthma (54 persons, 63%); and (3) not occupational/environmental exposure-related asthma (21 subjects, 24%). Two distinct clinical presentations of irritant-induced asthma emerged: the first was sudden onset (29 subjects) and the second was not so sudden in onset (25 subjects). Sudden-onset, irritant-induced asthma was analogous to the reactive airways dysfunction syndrome. Clinical manifestations began immediately or within a few hours (always within 24 h) following an accidental, brief, and massive exposure. In contrast, for the not-so-sudden-onset asthma subjects, the causative irritant exposure was not brief, usually not massive, continued for >24 h, and the initiation of asthma took longer to evolve. Eighty-eight percent of individuals with not-so-sudden irritant-induced asthma displayed an atopy/allergy status (p

Irritant-induced asthma signifies nonallergic asthma without latency or immunological sensitization. The acute sudden-onset type that appears within 24-h after a single, massive irritant gas, vapor, or fume exposure is coined Reactive Airways Dysfunction Syndrome (RADS). Almost all cases are accidental and arise without warning such as with an unanticipated explosion, accidental release of irritant(s) held under pressure, activities taking place in a confined space and/or emissions of smoke and irritant gases accompanying a fire. Presumably in some poorly understood manner, the massive irritant exposure leads to persistent airway inflammation, altered airway remodeling, sustained airway hyperresponsiveness and asthmatic symptoms. A second type of irritant-induced asthma emerges not as suddenly as RADS. Individuals are repeatedly exposed to non-massive levels of irritants over a few days, weeks, or months and eventually develop clinical asthma. Ostensibly, this type of asthma is associated with a preexisting susceptibility including asthma in clinical remission or stability. The long-term outcome of subjects with irritant-induced asthma is similar to subjects with allergic occupational asthma. The treatment of irritant-induced asthma is similar to the treatment afforded patients suffering with other types of adult-onset asthma.

Two types of occupational asthma have been identified and are distinguished by whether they appear after a latency period. Asthma without a latency period is best illustrated by irritant-induced asthma. The reactive airways dysfunction syndrome is a subset of irritant-induced asthma. Although case reports appeared in the literature before 1985, the term reactive airways dysfunction syndrome was coined in 1985. Since that report a number of case reports of asthma-like illnesses developing as the direct consequence of massive toxic inhalation exposure have been published. Not all experts, however, are certain that reactive airways dysfunction syndrome is a real and distinct clinical entity. Most studies and reviews, although acknowledging the current gap in our knowledge of the epidemiology, pathogenesis, and pathologic findings, conclude that the available scientific evidence supports the conclusion that reactive airways dysfunction syndrome and irritant-induced asthma are valid disorders.

is no scientific evidence whatsoever that this syndrome even exists. The majority of these people, we think, have other kinds of problems."' The following discussion will deal with host factors and susceptibility to adverse indoor air pollution. An important question is whether the persons affected derive their response because of some preexisting "sensitivity" or "susceptibility" that puts them at an increased risk for evolving symptoms from low levels of indoor air pollutants.

Clinical and research interests in occupational asthma increased dramatically in the 1980s. Advances in our knowledge base have led to improved recognition, management, and methods for preventing this disorder. An accelerated pace of basic and clinical research is anticipated in the 1990s. These efforts will likely lead to a more complete understanding of the disease (and pay dividends in understanding asthma itself). Occupational asthma is predicted to be the preeminent occupational lung disease in the next decade.

Although the electromechanical properties of, and the cholinergic innervation to adult airway smooth muscle has been extensively studied, the little information is available on developing human airway smooth muscle, and the role of cholinergic mechanisms in regulating bronchomotor tone. A total of 7 tracheae obtained at the time of elective abortion and between 12-16 weeks of gestational development were used in this study. For each trachea, muscle tension and transmembrane potentials were measured simultaneously using an isometric force transducer and a standard 3-M KCl-filled glass microelectrode. All preparations showed spontaneous electrical oscillations approximately 8 mV in amplitude, which could be increased using electrical field stimulation, or exogenously applied acetylcholine. This was accompanied by a corresponding increase in muscle tension. Atropine (0.1 microM) abolished this potentiation, but had no apparent effect on the oscillations. Slow-wave activity was completely suppressed in the absence of extracellular Ca2+, or in the presence of verapamil (1 microM) or quinidine (1 microM). It appears that these oscillations of membrane potential may be potentiated by cholinergic mechanisms which regulate cell membrane ion channels, thus serving to change excitability in a rhythmic manner.

A previous American College of Chest Physicians Consensus Statement on asthma in the workplace was published in 1995. The current Consensus Statement updates the previous one based on additional research that has been published since then, including findings relevant to preventive measures and work-exacerbated asthma (WEA).A panel of experts, including allergists, pulmonologists, and occupational medicine physicians, was convened to develop this Consensus Document on the diagnosis and management of work-related asthma (WRA), based in part on a systematic review, that was performed by the University of Alberta/Capital Health Evidence-Based Practice and was supplemented by additional published studies to 2007.The Consensus Document defined WRA to include occupational asthma (ie, asthma induced by sensitizer or irritant work exposures) and WEA (ie, preexisting or concurrent asthma worsened by work factors). The Consensus Document focuses on the diagnosis and management of WRA (including diagnostic tests, and work and compensation issues), as well as preventive measures. WRA should be considered in all individuals with new-onset or worsening asthma, and a careful occupational history should be obtained. Diagnostic tests such as serial peak flow recordings, methacholine challenge tests, immunologic tests, and specific inhalation challenge tests (if available), can increase diagnostic certainty. Since the prognosis is better with early diagnosis and appropriate intervention, effective preventive measures for other workers with exposure should be addressed.The substantial prevalence of WRA supports consideration of the diagnosis in all who present with new-onset or worsening asthma, followed by appropriate investigations and intervention including consideration of other exposed workers.

We examined the effects of a new anti-asthmatic drug, azelastine, and its principal metabolite, desmethylazelastine, on the in vitro electromechanical response of human airway smooth muscle during cholinergic stimulation. Membrane potential and isometric force were simultaneously measured using an intracellular microelectrode and a microforce transducer. Desmethylazelastine significantly suppressed acetylcholine-induced depolarization and contraction at 10(-6) M, whereas azelastine produced similar results at 10(-4) M, suggesting that the metabolite may be the principal compound acting upon the airway smooth muscle cell.

An investigation of a platinum refinery operation consisted of an administered questionnaire, spirometry, skin prick testing with platinum salts and common aeroallergens, serum total IgE, radioallergosorbent test for platinum salts, and measurement of nonspecific airway hyperresponsiveness by cold air challenge testing. Among 136 employees examined, there were 107 current and 29 medically terminated workers; 23 (17 percent) subjects had a positive platinum salts prick skin test and 19 (14 percent) displayed a positive cold air challenge. RAST binding for platinum salts IgE antibodies showed a high level of agreement with platinum skin prick test results. A proportion (63 percent) of the population (74 current and 12 terminated workers) underwent repeat platinum skin testing one year later. Among current workers, there was conversion of the platinum skin test from negative to a positive test in five employees, with three conversions occurring in workers who showed only a positive cold air challenge test the year before. Platinum skin sensitivity, asthma symptoms, and nonspecific airway hyperresponsiveness persisted for years after termination of exposure in some medically terminated workers presumably because of a delay in removal from work of employees who became sensitized to platinum salts. It is suggested that proper surveillance for occupational asthma involves the use of several testing procedures. Prompt removal from work of individuals found to become sensitized to platinum salts is important in this industry.

The specific causes and mechanism(s) for asthma occurring among occupants of non-residential buildings with poor indoor air quality are not known, but allergic and nonallergic processes are possible explanationsRepeated indoor air quality measurements were made while employees were working in a building where cigarette smoking was allowed. Seven of 19 employees who sought medical care from their private physicians because of respiratory complaints received a diagnosis of asthma. Subsequently, 19 symptomatic employees were examined at the University of South Florida (USF) 2 +/- 0.8 months (mean +/- SD) after removal from the building.The first floor of the building, where employee complaints were prevalent, was characterized by markedly reduced outdoor fresh air supply, diminished air circulation to the occupant spaces, and elevated airborne concentrations of formaldehyde. Nineteen workers examined at the USF 2 +/- 0.8 months after leaving the building reported ear, nose, and throat irritation and asthma-like symptoms while working in the building. There was resolution of symptoms in most of the seven employees (37%) with asthma previously diagnosed by their private physician. In fact, 16 of 19 subjects (84%) reported resolution or significant improvement of symptoms. Among 11 persons with symptoms suggesting asthma while working in the building, 4 persons (21%) showed a negative provocative concentration of methacholine producing a 20% fall in FEV1, including two subjects with doctor-diagnosed asthma.Confirmation of building-related asthma is influenced by time factors and the clinical criteria used for diagnosis. A nonallergic mechanism seems operative in our cases. While considered an example of occupational asthma, building-related asthma is a challenge for the practicing physician to confirm retrospectively.

A variety of factors influence exhaled breath nitric oxide (ENO) but few studies have examined ENO at the extremes of adult age. This investigation explores whether there is a difference in ENO between groups of older and younger individuals. A total of 48 normal subjects consisting of 23 younger (median age - 24 years) and 25 older (median age - 72 years) participants were studied. Carefully defined clinical and spirometric parameters, smoking history, and drug/medication documentation were determined to insure normalcy. Measurements of ENO were made using ATS/ERS recommended methodologies. The older group consistently showed higher ENO concentrations than-the younger subjects; median ENO values were 36.9 and 18.7 ppb, respectively (p < 0.001). The statistical significance held true when adjusting for multiple testing with the Holm method and accounting for outliers and medication usage. ENO levels are significantly higher in a normal older population. Comparing ENO between individuals at the extremes of age may depict differences more decidedly. Whether elevated ENO reflects underlying airway inflammation in older persons remains unanswered. It is possible that the difference in NO concentrations between older and younger groups represents only a marker of past oxidant exposures and holds no clinical significance. Additional investigations are necessary to elucidate the mechanisms and significances of elevated NO levels in the aged.

Background The National Institute for Occupational Safety and Health's (NIOSH) National Occupational Research Agenda (NORA), identified “exposure assessment methods” as a priority area for research in occupational medicine. Methods The University of South Florida Environmental Assessment Questionnaire (EAQ) describes exposures from the workers point of view. The questionnaire was distributed to a sample of workers drawn from a population of over 3,000 workers employed by a Florida food processing plant. The analysis of the validity was based on 211 subjects and the analysis of the reliability was based on 44 subjects. Results For the category scores, the sensitivities ranged from 0.67 to 1.0, the specificities ranged from 0.52 to 0.83, the positive predictive values ranged from 0.60 to 1.0, and the negative predictive values ranged from 0.55 to 1.0. All of the weighted kappas for the subcategories were above zero. The Spearman rank-order coefficients were above 0.5 for all of the exposure categories except the mold, plant, and animal exposure category which was 0.49. The correlation coefficient for the questionnaire as a whole was 0.85. Conclusions This study showed the EAQ as a whole to be reliable and valid. Gathering valid occupational exposure information with this method was both feasible and economical. Am. J. Ind. Med. 46:142–150, 2004. © 2004 Wiley-Liss, Inc.

Direct care-nursing personnel around the world report high numbers of work-related musculoskeletal disorders. This cross-sectional study examined the association between the performance of high-risk patient-handling tasks and self-reported musculoskeletal discomfort in 113 nursing staff members in a veterans' hospital within the United States. Sixty-two percent of subjects reported a 7-day prevalence of moderately severe musculoskeletal discomfort. There was a significant association between wrist and knee pain and the number of highest-risk patient-handling tasks performed per hour interacting with the load lifted. On units where lifting devices are readily available, musculoskeletal risk may have shifted to the wrist and knee.

David Wilson Talmage, one of the most important pioneers of the molecular biology of immunoregulation, in discussing recently (1988) what is beyond molecular immunology, poses the following questions: What will we study after we understand all the genes and their products that impact on the immune system? Surely, in a few years we will understand how lymphocytes differentiate and are activated, how they synthesize, secrete, kill, migrate. What will we study then? My prediction is that immunology will then have its greatest challenge. How can we put it all together for the benefit of mankind? How will we prevent allergies, autoimmunity, transplant rejection, and how will we cure cancer? The coming era of immunology will be a stage of synthesis–a return to Stage 1 and the immunology of the whole animal. [Talmage, 1988]

Occupational asthma is an important occupational respiratory disorder, both in terms of morbidity, disability and in the total number of cases. The two types of occupational asthma are classified on the basis of their temporal relationship to onset. Occupational asthma with latency reflects allergic occupational asthma and is a condition characterized by a preceding latent period of workplace exposure during which allergic sensitization to a material present at the work site occurs. It is characterized biochemically by immunologic alterations and physiologically by variable and work-related airflow limitation with the presence of both specific and nonspecific airway hyperresponsiveness. In contrast, occupational asthma without latency is an asthmatic condition that develops suddenly and without a preceding latent period, as epitomized by the reactive airways dysfunction syndrome (RADS). RADS is distinguished physiologically by chronic, persistent nonspecific airway hyperresponsiveness and usually occurs after a single brief high-level exposure to an irritant gas, vapor of fume; new information suggests that a more prolonged irritant exposure, in certain susceptible persons with a pre-existing allergic predisposition, can also lead to the initiation of new-onset asthma. The factors that may be influential in the pathogenesis of occupational asthma include: exposure characteristics, industrial factors, job attributes, geographic and climatic conditions, economic considerations and personal or host conditions, such as atopy and cigarette smoking. Preventive measures and opportunities for intervention are essential and must address plans for reducing or eliminating accidents and spills, as well as plans for engineering control methods and proper and effective local exhaust ventilation. Medical surveillance programs are the keystone for prevention and should identify persons who are at an increased risk for developing occupational asthma, as well as detecting asthma at an early stage when intervention options are likely to be successful. For sensitized workers, the best preventive option is completed removal from the work environment.

A case-control study was conducted of the risk of lung cancer and mesothelioma from environmental and occupational exposures associated with sugarcane production. A slight, not statistically significant, excess risk of lung cancer was observed among participants who reported working in the sugarcane industry (odds ratio 1.8, 95% confidence interval 0.5–7.5). No increased risk was observed among our population, associated with living near sugarcane growing areas. Little difference was observed between cases and controls in years employed in the industry or jobs performed. Only one mesothelioma case and no controls reported working in the sugarcane industry.

Crude preparations of brevetoxin (PBTX) produce airway contraction; however, it is not known if this toxin-induced mechanical response is coupled to changes in airway smooth muscle membrane potential. Membrane potentials and contractility of in vitro canine trachealis smooth muscle preparations were simultaneously measured with a microelectrode and microforce transducer before and during exposure to either the crude toxin (0.01–1.2 μg/ml), or the purified fractions PBTX-2 or PBTX-3 (0.01–0.07 μg/ml). Membrane potentials in cultured airway smooth muscle-reaggregate preparations were similarly studied. Toxins produced concentration-dependent depolarizations and contractions in in vitro preparations. These responses were not obtained in the presence of either the muscarinic blocking agent atropine, the sodium channel blocker tetrodotoxin (TTX), 0 mM extracellular Ca 2+ , or the Ca 2+ channel blocker verapamil. The toxins were without effect in cultured cells, whereas acetylcholine produced depolarizations which were blocked in the presence of atropine, but not TTX. This suggested the presence of functional cholinergic receptors in cultured cells, and the PBTX-induced release of endogenous acetylcholine from peripheral nerve endings in the in vitro airway smooth muscle response.

Airway reactivity and disease severity were investigated in 24 subjects with stable chronic bronchial asthma. Disease severity was determined by assigning a disease severity score (DSS) representing six clinical and therapeutic parameters. Airway hyperresponsiveness was assessed in two ways: airway reactivity score (ARS) based on the number of positive responses to a question concerning exposure to 22 nonspecific inhaled irritants and methacholine challenge testing and determining the cumulative dose causing a 20% reduction in FEV2 (CMD20). A significant correlation between DDS and CMD20 (r = 0.57; p less than 0.003) and DSS and ARS (r = 0.67; p less than 0.0003) attested to the important influence of airway hyperresponsiveness on disease severity. Significant correlations for ARS with CMD20 (r = -0.60; p less than 0.002) suggested the consistency with which the ARS estimated methacholine hyperresponsiveness. We found no statistically significant correlations between DSS, ARS, or CMD20 and the age of subject, duration of asthma, or other host characteristics. There was not a significant correlation between the degree of airway obstruction and DSS or ARS noted. The results of this investigation demonstrate the value of the use of clinical information for assessing airway hyperresponsiveness and disease severity in patients with chronic stable asthma. Both ARS and DSS are useful clinical tools for estimating methacholine reactivity.

Abnormalities of second-wave platelet aggregation were demonstrated in 17 of 33 asthmatic patients in whom drug and diet intake were controlled in the hospital. Mean abnormal responses were significantly greater after epinephrine- (p less than 0.001), adenosine diphosphate-(less than 0.001), collagen- (p = 0.01), and thrombin- (p less than 0.001) induced platelet aggregation in patients with immunologically mediated asthma and serum IgE levels greater than 250 U/ml as compared to patients without immunologic factors and/or normal controls. Mean pollen-specific radioallergosorbent (RAST) binding was also significantly higher in patients with abnormal aggregation as compared to normal platelet responders (p = 0.02). Release of serotonin generally reflected abnormal aggregation patterns in asthmatic patients. Platelet factor 4 release was significantly decreased in the same groups of patients. These results suggest that the allergic state may affect platelet membrane responsiveness to multiple aggregating agents.

The effects of moderate concentrations of ethanol (8-34 mM) on the electromechanical activity of airway smooth muscle cells of canine trachealis, stimulated by the spasmogen tetraethylammonium (TEA), are described for in vitro and cultured reaggregate preparations. Ethanol produced a concentration-dependent hyperpolarization, and suppression of action potentials in smooth muscle preparations, in vitro, whereas it was without effect in cultured airway smooth muscle cells. In the presence of the beta-adrenoceptor antagonist propranolol (1 microM), ethanol had no effect on in vitro preparations. Isoproterenol (0.1 microM) produced hyperpolarization and suppression of action potentials in airway smooth muscle of both preparations. These effects were not observed when propranolol was additionally present. This suggests that both in vitro, and cultured airway smooth muscle preparations maintained their beta-receptors, and that ethanol caused the release of endogenous catecholamine from adrenergic nerve endings which apparently remained intact in in vitro, but not in cultured airway smooth muscle preparations.

A lead-intoxicated patient with extremely high blood lead levels and unexpectedly mild symptoms was studied prior to and following treatment with calcium disodium edetate (ethylenediaminetetraacetic acid) and then prior to and following oral administration of zinc sulfate. During chelation therapy, erythrocyte (delta)-aminolevulinic acid dehydratase (ALAD) activity decreased as blood lead levels fell. Urinary excretion of zinc increased and was more than 3.5 times greater than that of lead. The ratio of blood lead to serum zinc was greatest (1.47) when ALAD activity was lowest. Oral administration of zinc sulfate following chelation therapy resulted in a significant increase in mean ALAD activity. In vitro additions of zinc chloride to the patient's erythrocytes resulted in reactivation of ALAD activity. These studies suggest that zinc is an important element in the ALAD system in man. Zinc may play a protective role in lead toxicity, and zinc supplementation may be a useful adjunct to chelation therapy for lead toxicity.