Occupational upper airway disease

Clin Chest Med 23 (2002) 717 – 725

Occupational upper airway disease Ron Balkissoon, MD, MSc National Jewish Medical and Research Center, 1400 Jackson Street, Denver,CO 80206, USA

A variety of industrial chemicals has been associated with upper airway irritation or allergic reactions [1 – 6]. Table 1 lists some of the common industrial irritants that are known to be associated with rhinitis or sinusitis. Although it is recognized that occupational allergens can lead to laryngeal edema with consequent respiratory compromise [7], it was only recently reported by Perkner and colleagues [8] that irritant exposures may lead to laryngeal or vocal cord dysfunction. Occupationally-induced upper and lower airway disorders may coexist; many of these agents traverse the upper and lower airways and exert immune irritant effects at both levels. This article focuses on our current understanding of nasal and laryngeal responses to irritant and allergenic agents in the workplace and how this information influences a rational approach to diagnosis and treatment of these disorders.

Structure and function of the upper airway As inspired air travels through the upper airway, its temperature is adjusted to near body temperature, and its relative humidity is brought to between 75% and 80%. The vascular supply of the nose has a central role in regulating temperature and humidity for the respiratory tract. The nasal passages have a diurnal variation in patency that alternates between the two sides (the so-called ‘‘nasal cycle’’) and results in cyclical changes in airflow from left and right nares. In most circumstances, nasal congestion is primarily a vascular phenomenon whereby plasma transudation into the interstitium and dilation of post-capillary venules (‘‘venous sinusoids’’) result in reversible soft

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tissue engorgement. Superimposed on this natural physiological variability, allergens and chemical irritants are capable of producing acute or chronic nasal congestion and rhinorrhea in susceptible individuals. Inspired particles (>10 mm) are usually deposited in the upper airway through the process of ‘‘impaction’’. The cilia sweep mucus and particles posteriorly into the pharynx to be swallowed or expectorated. Constituents of the glandular secretions possess antibacterial activity (lactoferrin, lysozyme, and IgA) as do plasma components (uric acid, IgG, and albumin). Glandular secretions and plasma transudation are stimulated by autonomic activity, mast cell degranulation, and neuropeptides [9, 10]. Water-soluble gases and vapors (including such irritants as ammonia, formaldehyde, and organic acids) usually dissolve in the upper airway. Agents that are less water-soluble, such as nitrogen dioxide and phosgene, travel distally before being absorbed and can result in delayed onset chemical pneumonitis (Fig. 1). The upper respiratory tract senses olfactory stimuli (cranial nerve I) and mechanical, thermal, and chemical irritant stimuli through afferent branches of the trigeminal, hypoglossal, and vagus nerves. Unmyelinated c and A-d fibers respond to capsaicin, hydrogen ions, and reactive chemical agents. It remains unclear whether nasal congestion and rhinorrhea can be caused by inhaled irritants triggering parasympathetic or local axonal reflexes. The larynx has three major physiological functions: maintenance of an airway, protection of the airway, and phonation. The cough reflex and laryngeal closure reflex are important for protecting the airway during deglutition but also in response to potentially noxious inhaled stimuli. The cartilage, muscles, and nerves of the larynx work in a coordinated fashion to facilitate speech, breathing, coughing, and swallowing. The

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Table 1 Selected occupational irritants Occupation

Irritant

Agricultural workers Custodians Firefighters Food service workers Health professionals Laboratory workers Military personnel Power plant and oil refinery workers Printers, painters Pulp mill workers Railroad personnel, miners, truck drivers Refrigeration workers (commercial) Roofers, pavers Swimming pool service workers Waste water treatment workers Welders Woodworkers

Ammonia, nitrogen dioxide, hydrogen sulfide Ammonia, bleach (hypochlorite), chloramines Smoke, hazardous materials releases Cooking vapors, cigarette smoke Glutaraldehyde, formaldehyde Solvent vapors, inorganic acid vapors/mists Zinc chloride smoke Sulfur dioxide Solvent vapors Chlorine, chlorine dioxide, hydrogen sulfide Diesel exhaust Ammonia Asphalt vapors, PAHsa Chlorine (hypochlorite), hydrogen chloride Chlorine, hydrogen sulfide Metalic oxide fumes, nitrogen oxides, ozone Wood dust

a

Polycyclic aromatic hydrocarbons (also skin and lung carcinogen)

upper respiratory tract defends the lower respiratory tract against inhalation insults by several mechanisms. Reflex responses to irritant stimuli include mucus secretion, cough, sneeze, glottic closure, apnea, and increases in bronchomotor tone. The neural reflex arcs

for these responses remain poorly defined, however. Glottic closure is mediated by the superior laryngeal (afferent), recurrent laryngeal, or vagal nerves (efferent). Irritant-induced bronchomotor reflexes (bronchoconstriction) are mediated by the vagus nerve [11].

Fig. 1. Water solubility and site of initial impact of irritants. From US Department of Health and Human Services, Surgeon General’s Office: The Health Consequences of Involuntary Smoking. 1986.

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Occupational allergic rhinitis

Table 2 Agents that produce occupational allergic rhinitisa

Pathophysiology General class Specific agent

The upper airway may respond to environmental stimuli through allergic or neurogenic mechanisms. Inflammatory changes in the upper airway may lead to rhinitis, sinusitis, pharyngitis, or laryngitis. Rhinitis has been divided into allergic and nonallergic subcategories (Box 1). Individuals who are suspected of having allergic or nonallergic rhinitis report increased congestion after exposure to airborne irritants such as cigarette smoke, perfumes, cleaning agents, and temperature/humidity changes not unlike the bronchial hyperresponsiveness of asthmatics [12]. Rhinitis caused by dramatic (high-level) irritant exposures was described by Meggs [13] as ‘‘reactive upper airway dysfunction syndrome’’ (RUDS) [13] that is analogous to the corresponding form of irritantinduced asthma, known as reactive airways dysfunction syndrome or (RADS). Biopsies of the nasal mucosa from individuals who were acutely exposed to irritants showed epithelial desquamation, defective epithelial cell junctions, and increased numbers of nerve fibers, but no significant change in neuropeptides [14]. The irritant (nociceptor) receptor system of the trigeminal nerve contains Ad and c-fibers that give rise to local (neuropeptide-mediated) and central (parasympathetic and sympathetic) reflexes following irritant stimulation [15,16]. Meggs [17] proposed that the systemic symptoms of ‘‘chemical sensitivity’’

Box 1. Subcategories of rhinitis Allergic rhinitisa Seasonal Perennial Nonallergic rhinitis ‘‘Vasomotor’’a Irritanta Gustatory Nonallergic rhinitis with eosinophilia syndrome (NARES) Rhinitis medicamentosa Atrophic Infectious Endocrine a

Has potential occupational triggers

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High molecular weight

Low molecular weight

Baking flour; alpha amylase Animal proteins (urinary, salivary)

Examples of occupation affected Bakers

Laboratory animal handlers Veterinary personnel Proteolytic enzymes Detergent manufacturers Mold spores Librarians; composters Insect antigens Flood control workers Pharmaceutical workers (antigen preparation) Natural rubber latex Health care personnel Food service workers Florists Trimellitic anhdride Fabricators (various) (epoxy component) Di-isocyanates Auto body painters (polyurethane Boatbuilders component) Shipping clerks Sawyers Plicatic acid (from western red cedar) Abietic acid/ Solderers (electronics) collophony (from rosin core solder)

a These agents are also generally linked with occupational asthma

syndromes (eg, headache, nausea, fatigue, myalgias, confusion, and so forth) that are often seen in patients with RUDS may be caused by circulating neuropeptides, cytokines, or ‘‘neurogenic switching’’. Workplace allergens that produce allergic rhinoconjunctivitis may be: (1) common inhalant allergens that are incidentally encountered at work (eg, cat dander, dust mite, grass pollen); (2) allergens that are more common at work but that are also found outside of work (eg, latex, flour); or (3) unusual agents that are encountered only in industrial environments (eg, trimellitic anhydride, isocyanates). A short list of some of the many agents that produce occupational allergic rhinitis are shown in Table 2. Because these agents are known to produce occupational asthma, it is not unusual for sensitized individuals to have occupational asthma and rhinitis. Bioaerosols that are generated from water-damaged areas or pooled water sources are a potential cause of allergic or infectious rhinosinusitis and conjunctivitis. Thus, as is the case with asthma, occupational allergic rhinitis may be aggravated by, or caused by, work.

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Clinical management The diagnosis of occupational allergic rhinitis is a clinical diagnosis that combines information from history, physical examination, and laboratory testing. The history is characterized by symptoms that include sneezing, itching, rhinorrhea, and congestion, with or without associated eye and chest symptoms. Occupational allergic rhinitis may exhibit seasonal variation; however, this pattern is more common in perennial rhinitis. Individuals who have occupational allergic rhinitis may be sensitized to workplace and nonworkplace antigens. Hence with these factors complicating the interpretation of temporal relationships between work exposure and symptoms, the absence of a clear work relationship cannot rule out occupational causes. Physical examination often reveals a pale, boggy nasal mucosa. Laboratory testing may include a complete blood count or nasal smear that demonstrate eosinophilia, increased serum total IgE, and increased in vitro (RAST or ELISA) work antigen-specific IgE. Skin prick testing, with saline and histamine controls, is helpful when extracts are available for workplace allergens; otherwise, response to occupational allergen avoidance may provide the best evidence for a work relationship. Nasal inspiratory peak flow measurements may provide objective validation of crossshift symptoms. Nasal peak flows can be used during consecutive periods of allergen avoidance and normal work routine to help establish an occupational cause; however, they have the same limitations of peak flow monitoring that are used to assess occupational asthma. Though rarely used (and not standardized), specific nasal inhalation challenges to occupational allergens, with measurements of nasal resistance or inflammatory responses, can be employed, not unlike challenges performed to assess occupational asthma. Identification of an individual with occupational allergic rhinitis should act as a sentinel health event to alert employers to the potential risk for occupational asthma to develop in the primary case and coworkers. In such settings, engineering controls (isolation, ventilation) or substitution strategies should be used as methods of primary prevention of sensitization. Treatment should include allergen avoidance where possible, for the control of nasal symptoms and to prevent the progression to asthma. Substitution of the causative agent or reassignment are advisable where practical. Engineering controls and personal protective equipment are unlikely to provide adequate control of antigen exposure. A particularly challenging situation presents itself in health care settings. Individuals, with respiratory allergies, who are sensitive to latex must avoid latex gloves and should

avoid working in areas where others wear powdered latex gloves (the powder serves as a carrier for latex antigen). Mainstays of pharmacotherapy for allergic rhinitis are the same for occupational and nonoccupational variants and include systemic antihistamines, nasal steroids, the mast cell stabilizer (cromolyn sodium), inhaled antihistamines (Azelastine), and anticholinergics (ipratropium bromide). The efficacy of desensitization therapy has not been established for most occupational sensitizers. Data exist that link increased nasal congestion and obstructive sleep apnea [18 – 20]. This association may explain some of the neurocognitive and musculoskeletal (fibromyalgia) symptoms, that are often attributed to ‘‘multiple chemical sensitivity’’ syndromes, in individuals with irritant rhinitis.

Occupational irritant rhinitis Chemical irritants in office environments include combustion products from tobacco smoke and malfunctioning appliances, and volatile organic compounds from cleaning products, office supplies and machines, building materials, and furnishings. Industrial settings present workers with an even wider range of airborne irritants. Extreme forms of industrial irritant rhinitis occur in electroplaters and others who are exposed to chromic acid, which may cause nasal mucosal ulcerations and even septal perforation. Diagnostically, it can be challenging to differentiate between irritant, allergic, or infectious rhinitis. The report of predominantly irritant symptoms (dryness and pain or burning, rather than itching or sneezing) and dramatic improvement during times away from work support the diagnosis of irritant rhinitis. One must be cognizant of the fact, however, that persons with allergic rhinitis are more sensitive to irritants as environmental tobacco smoke, volatile organic compounds, and chlorine gas [21 – 23]. This situation complicates the differentiation of work-induced irritant rhinitis and nonoccupational allergic rhinitis aggravated by workplace exposures. Physical examination that reveals erythema of the mucous membranes, particularly punctate erosions of the nasal mucosa, supports an irritant process, but is neither sensitive nor specific. Laboratory evaluation in patients with irritant rhinitis shows absence of systemic eosinophilia, a normal total serum IgE, predominance of neutrophils on nasal smear, and negative immunological studies (skin prick test or RAST) for workplace allergens. Treatment for occupational irritant rhinitis, whether caused by chronic or acute exposure (RUDS), consists

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of reduction of exposure, nonspecific supportive measures (eg, saline nasal lavage), and occasionally, topical steroids. Patients who are troubled by prominent reflex symptoms (eg, congestion and rhinorrhea) may benefit from the topical anticholinergic, ipratropium bromide. In patients with atopy, control of allergic rhinitis, whether occupational or nonoccupational, may also decrease reactivity to chemical irritants, although this issue has not been well-studied. Occupational vasomotor rhinitis, a subcategory of nonallergic rhinitis, is a term that is sometimes used to describe augmented nasal reactivity to nonspecific physical stimuli at work. Symptoms of rhinorrhea usually predominate. Relevant physical stimuli include low humidity, extremes or rapid changes in temperature, and excessive air motion. Chemical irritant exposures may also be triggers for vasomotor rhinitis. Treatment of occupational vasomotor rhinitis is similar to other forms of rhinitis. Ipratropium bromide may be particularly effective [24].

Sinusitis Relatively few studies examined sinusitis related to occupational exposures. Surveys of furriers, spice workers, vegetable picklers, hemp workers, and grain and flour workers revealed increased prevalence rates of self-reported sinusitis symptoms [25,26]. Clinically, a worker who recounts a history of apparent occupational rhinitis followed by sinusitis that is refractory to antibiotic treatment should be reassessed from the standpoint of allergen or irritant avoidance.

Occupational irritant-induced vocal cord dysfunction Pathophysiology Much more is known about the mechanisms of allergen-mediated laryngeal dysfunction than that following irritant exposure. Allergen-induced laryngeal edema is seen as part of the cascade of immuneregulated inflammatory events of Type I hypersensitivity reactions [7]. Following allergen exposure, sensitized individuals will develop typical mast cell and IgE-mediated, immune responses that lead to swelling of the laryngeal structures with consequent symptoms of upper airway obstruction, and possibly, other systemic manifestations of TH2-mediated allergic response. In contrast, the pathophysiology of irritant-induced vocal cord dysfunction remains unknown. One hypo-

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thesis is that olfactory nerve stimulation or direct stimulation of nociceptive sensory nerve endings in the upper and lower respiratory tract may initiate local reflex arcs or higher center processing that lead to paradoxical laryngeal closure during inspiratory or expiratory efforts. It is plausible that following acute or chronic airway inhalational injuries there is a change in the number and/or regulation of sensory nerve endings that somehow lowers the threshold for initiating the glottic closure reflex to protect the lower airways from noxious exposures. Irritant stimulation of the nasal mucosa was reported to cause complete laryngeal closure [27,28]. Nasal stimulation by histamine is known to cause bronchoconstriction but also can cause expiratory laryngeal closure in the normal healthy population, as well as people with asthma or chronic bronchitis [11]. Irritant exposures via the mouth (as compared with the nose) are more likely to cause bronchoconstriction; this suggests that the main bronchoconstrictor effect may be influenced by laryngeal irritation rather than nasal irritation [11]. Morrison et al [29] recently proposed the term ‘‘irritable larynx syndrome’’ to describe individuals with episodic respiratory compromise that followed irritant exposures. Variable clinical manifestations included vocal cord dysfunction, cough, muscle tension dysphonia, and globus sensation. Borrowing from the chronic pain literature, they proposed that chronic nociceptive (irritant or pain) stimulation can lead to neural ‘‘plastic’’ changes in central neurons, thus lowering their threshold for stimulating the glottic closure reflex. The consequence of this lowered threshold is increased cough, laryngospasm, or paradoxical closure at relatively low irritant levels for affected individuals compared with controls. Although it is an intriguing and interesting hypothesis, it remains unproven and requires study. The rise in subglottic pressure against a closed glottis is important for the cough reflex and also provides a form of auto PEEP by increasing intraalveolar pressure. This effect has been used by severe asthmatics and those with emphysema to prevent premature airway collapse or closure. In individuals with emphysema or severe asthma, isolated late expiratory closure of the vocal cords may be a physiological adaptation to prevent or reduce early airway collapse during exhalation and thus promote better emptying of air from the lungs. These observations led to the hypothesis that the glottic closure reflex is somehow accentuated in persons who have vocal cord dysfunction (VCD), such that various extrinsic and intrinsic stimuli can trigger reflex closure of the vocal cords as an adaptive

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protective response. This may be an augmentation of a normal physiological response by lowering the threshold levels for initiation of vocal cord closure compared with normal individuals. Chronic irritation of the larynx, from gastroesophageal reflux disease, post nasal drip, or inhaled irritant exposures with consequent frequent throat clearing and cough, predisposes it to increased sensitivity to various external stimuli that trigger VCD attacks [29,30]. Clinical management Perkner and colleagues [8] showed that patients with irritant-associated vocal cord dysfunction, who reported that the onset of symptoms followed highlevel exposures to workplace irritant fumes or vapors, were initially misdiagnosed with RADS. Following the initial high-level irritant insult, patients developed recurrent wheeze, cough, and shortness of breath triggered by exposure to irritants such as cigarette smoke, cold air, exercise, perfume, cleaning agents, and other chemical odors. Headache, nausea, and light-headedness also occured. Symptoms that are more specific for VCD included sensations of choking or throat tightness, voice changes, inspiratory stridor, and greater difficulty getting air in than out. Many patients with VCD point to or grab their throat when describing symptoms. Reports of poor responses to bronchodilator medicines and inhaled or systemic steroids should raise suspicion of VCD. It was proposed, but not proven, that chronic rhinosinusitis with postnasal drip or gastroesophageal reflux disease may be a source of recurrent irritation to the larynx and lower airways that leads to increased laryngeal sensitivity to a variety of nonspecific stimuli[8, 30]. In the study by Perkner et al [8], central chest pain was a feature that distinguished this group from patients with nonoccupational VCD. This chest pain may be a manifestation of gastroesophageal reflux disease that is often associated with VCD or may be a direct result of trachobronchial injury caused by inhalation of noxious agents. The physical examination for VCD is fairly nonspecific. Laryngeal wheezing or stridor may not be present unless the patient is having an acute attack. Pulsus paradoxus and use of accessory muscles may be present in patients with acute, severe VCD. There may be evidence of rhinosinusitis (nasal congestion, exudate in posterior oropharynx, facial tenderness), or GERD (halitosis or epigastric tenderness). During symptomatic periods, spirometry typically demonstrates truncation or irregularity of the inspiratory or expiratory limbs of the flow volume loop; this suggests variable upper airway obstruction (see Fig. 3).

Spirometry and flow volume loops may be completely normal during asymptomatic periods. Presuming that VCD was primarily an inspirator phenomenon previous investigators described a forced expiratory flow at 50% forced vital capacity/forced inspiratory flow at 50% forced vital capacity (FEF50/FIF50) ratio (or mid expiratory flow/mid inspiratory flow [MEF/MIF]) greater than one as a characteristic feature of VCD [31 – 33]. Patients who have irritant-induced VCD frequently have irregularities in the expiratory limb of their flow volume loop. Hence, in the setting of inspiratory and expiratory truncation the FEF50/FIF50 is not a useful parameter to identify individuals with VCD. Bucca and coworkers [33] demonstrated that a

Fig. 3. (A) A normal flow volume loop. (B) Extrathoracic airflow obstruction with truncation of the inspiratory loop. This is consistent with symptomatic VCD but may be seen in other laryngeal diseases. FVC, forced vital capacity; FIF50, forced inspiratory flow at 50% forced vital capacity; FEF50, forced expiratory flow at 50% forced vital capacity. From Perkner J, Fennelly K, Balkissoon R, et al. Irritant associated vocal cord dysfunction. J Occup Environ Med 1998;40:136 – 43; with permission.

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greater than 25% drop in the MIF during histamine inhalation challenge was correlated with changes in mid-inspiratory, glottic cross-sectional area . Tests of bronchial hyperresponsiveness with methacholine or histamine may be negative or positive provocation concentration of methacholine causing a 20% drop in FEV1 from baseline (FEV1 PC20 <8 mg/ ml), with evidence of truncation of the flow volume loops during the challenge. Methacholine may be used as a nonspecific irritant stimulus to induce an acute VCD episode. Patients with VCD often show evidence of paradoxical or abnormal vocal cord movement during the inspiratory or expiratory phase of breathing during laryngoscopy following methacholine challenge, compared with persons without VCD (Fig. 4) [33]. If methacholine inhalation challenge fails to elicit VCD in individuals with a compelling history, irritant provocation tests with agents reported to cause symptoms may be useful. An acoustic reflectance device, which measures the cross-sectional area of the respiratory tract during

Fig. 4. The appearance of the vocal cords during (A) inspiration in a healthy patient and (B) during inspiration in a patient with VCD, showing the adduction of the vocal cords with the characteristic posterior ‘‘chink’’ opening. Illustration by Leigh Landskroner. From Perkner J, Fennelly K, Balkissoon R, et al. Irritant associated vocal cord dysfunction. J Occup Environ Med 1998;40:136 – 43; with permission.

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the inspiratory and expiratory phases of breathing, may have diagnostic usefulness. Although the technique requires further validation, it is relatively noninvasive and avoids potential laryngeal closure caused by direct irritation by the laryngoscope. In preliminary work with this device we detected dynamic narrowing of vocal cords and the extrathoracic trachea just below the vocal cords during forced vital capacity maneuvers. Imaging studies are generally not helpful in the evaluation of VCD. Patients with pure VCD have normal chest radiographs with no evidence of hyperinflation. Recent reports that used fluoroscopic and ultrasound imaging during stridorous events demonstrated vocal cord adduction during inspiration [34 – 36]. Imaging of the upper airway by CT scan was evaluated for upper airway obstruction in patients with sleep apnea but has not been applied to patients with VCD [37]. Long-term management of individuals with upper airway dysfunction requires a multidisciplinary approach. Physicians (who may include pulmonologists, occupational medicine specialists, otolaryngologists, allergists, or psychiatrists), voice pathologists, psychosocial staff, rehabilitation staff, and vocational counselors may play useful roles in the treatment of these patients. Voice pathologists/therapists, who provide instruction in techniques of throat relaxation, cough suppression, and throat clearing suppression, play a central role in managing VCD; we remain uncertain of the efficacy of this treatment. Too often, wellmeaning but ill-prepared speech therapists attempt to apply general methods that are not specifically targeted for VCD, with minimal success. This circumstance may frustrate the patient and the therapist. Voice pathologists may be helpful in the development and performance of desensitization protocols. Individuals are exposed to increasing concentrations of a provocative agent and coached by the therapist on how to control their laryngeal response or how to interrupt an acute attack. Psychosocial assessment and treatment is key in managing patients with IVCD because there is generally some degree (though highly variable) of psychological overlay, either preexisting or as a result of the consequences of developing work-related VCD. Input from psychologists or psychiatrists about evidence of conversion, panic, anxiety, affective, personality, or post traumatic stress disorders is helpful. Vocal cord dysfunction is a highly controversial and under-recognized disorder. The fact that many of these individuals are often misdiagnosed for years, and develop iatrogenic complications related to ster-

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oid therapy without significant benefit, adds to the psychological dimension of these cases. Hence, patient education and reassurance are extremely important. Follow-up with supportive counseling and teaching relaxation or biofeedback techniques may be beneficial. Clinicians should discontinue unnecessary medications such as bronchodilators and steroids if coexistent asthma has been ruled out. Treatment for associated GERD or rhinosinusitis may reduce symptoms. Workers compensation and vocational rehabilitation counseling are key aspects in the comprehensive management of these cases. Theoretically, most of these individuals should be able to return to work after several months of irritant exposure avoidance and therapy, with restrictions to avoid excessively high irritant exposures. Our experience has been that returning these individuals to their previous jobs has been challenging for psychological as well as medical reasons. Acute, severe episodes of VCD may generally be controlled and managed with sedation, or Heliox (80% helium/20% oxygen) [38,39]. Recent studies suggested that a simple continuous positive airway pressure-type device that provides intermittent, positive pressure can resolve an attack [40]. Topical lidocaine applied to the larynx may be useful during acute episodes in select patients. In severe cases, superior laryngeal blocks with clostridium botulinum toxin were attempted with variable success [41]. We have not generally found this treatment helpful for VCD; it is more successful for alleviating muscle tension dysphonia that may sometime accompany VCD [42]. Tracheotomy was performed on a few patients with severe classic VCD refractory to conventional therapy; however, it is rarely, if ever, indicated.

Summary The upper airway plays a critical role in filtering and conditioning air for the lungs. It provides the first line of warning and defense against microbials, allergens, and toxic inhalants. Current evidence suggests that the upper airway is susceptible to many of the pathogenic processes that the agents cause in the lower respiratory tract. Work-related rhinosinusitis or vocal cord dysfunction should prompt physicians and employers to identify the injurious agent(s) and formulate strategies to eliminate or reduce such exposures. Improving the work environment will prevent the development of new cases and the worsening of symptoms in existing cases.

Acknowledgements Thanks to Dr. Dennis Shusterman for review of this manuscript and to Ms Jen Shindoll for her assistance in preparation of the manuscript.

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