Irritants, Irritancy and Irritant Induced Asthma
Received Date: Feb 09, 2018 / Accepted Date: Feb 18, 2018 / Published Date: Feb 25, 2018
An irritant represents a non-corrosive chemical that causes a reversible non-immunologic inflammatory reaction after direct contact with the skin, eyes, nose and/or respiratory system. There are numerous reactions to irritants including change in spirometry, elevated exhaled breath levels of nitric oxide, enhancement of the response to allergen provocation and alteration of antioxidant defenses. Irritancy prompts an “inflammatory soup” of signaling molecules leading to tissue changes characterized by infiltration of mononuclear inflammatory cells, vascular congestion, augmented blood flow, contiguous edema with leaking of plasma, glandular hyper secretion and nervous hyperresponsiveness. Acute irritant-induced asthma, also referred to as Reactive Airways Dysfunction Syndrome (RADS), is a non-allergic type of asthma presenting without a prior time-period of latency. The manifestations of RADS begin within 24 h following a single massive exposure to an irritating gas, vapor or fume resulting in continuing airway inflammation, changed airway remodeling, persistent structural changes, neural disturbances and unrelenting airway hyperresponsiveness. Recommendation is that RADS or any serious inhalation exposure be handled in a hospital setting. Serial bronchoscopic assessments assist management decisions. Management requires astute judgment and skill for a rapidly changing clinical scenario. The influence of odors and emotion in the pathogenesis irritant-induced inhalational responses is significant.
Keywords: RADS; Irritants; Irritancy; Inhalation injury; Asthma, Irritant-induced asthma; Reactive Airways Dysfunction Syndrome (RADS); Airway hyper responsiveness; Odors; Odorants
Accidental irritant exposures may cause workplace and public health consequences as well as producing devastating population impacts [1,2]. In 1989, the Occupational Safety and Health Administration (OSHA), with a consensus by the American Conference of Governmental Industrial Hygienists (ACGIH), promulgate a workplace exposure limit for irritants based on objective signs of irritation . The role of odors, as an indicator of a serious irritant exposure, may complicate cases of inhalational grievances [3-8]. Because of their pervasiveness, a better understanding of and preventive strategies for irritant exposures are indispensable [9,10].
A practical definition of an irritant is a non-corrosive agent that causes a reversible non-immunologic inflammatory reaction after direct contact with the skin, eyes, nose, throat and/or lower respiratory system . There is the consideration that irritants are chemicals; but, mechanical, thermal and radiation stimuli (i.e., ionizing radiations) are also irritants. Irritant releases follow a high-level irritant delivery, after repeated low-level discharges or by a mixture of both . Radiationinduced tissue damage leads to the generation of short-lived free radicals, changes in cellular DNA, and incitement of an inflammatory response involving proinflammatory cytokines, chemokines, receptor tyrosine kinase, and adhesions molecules . Initially, there is rapid proliferation and maturation of basal keratinocytes, hair follicle stem cells and melanocytes. Additional exposure to radiation results in further direct tissue injury, inflammation, and impaired epithelial regeneration. Table 1 lists a range of irritants and their origins . Sometimes an allergen and irritant interact to create an incomplete antigen (i.e., hapten) with similar properties as the original allergen. In this circumstance, there is instigation of an immune-mediated reaction [15,16].
|Exposure||Agent or process|
|Acids||Glacial acetic, sulfuric acid, sulfurous acid, hydrochloric acid, hydrofluoric acid, hydrofluoric acid, acetic acid, sulfur trioxide|
|Alkali||Bleach, lye, lime, calcium oxide, ammonia compounds, sodium hydroxide, World Trade Center dust, air bag emissions|
|Gases||Chlorine, sulfur dioxide, ammonia, mustard, ozone, hydrogen sulfide, phosgene, nitrogen dioxide|
|Spraying||Spraying of bleach, paints and coatings|
|Explosion||Irritant gases, vapors and fume releases under pressure|
|Fire/pyrolysis||Combustion and pyrolysis products of fires, burning paint fumes, pyrolysis products of polyvinylchloride (PVC) meat wrapping film; smoke inhalation|
|Confined spaces||Epichlorhydrin, acrolein, floor sealant, metal coating remover, biocides, fumigating aerosol, cleaning aerosol sprays, mixture of drain cleaning agents|
|Workplace||Glass bottle making workers; popcorn flavoring makers; second hand tobacco smoke; chlorine gas puffs; pyrite dust explosion; ozone used a disinfectant; locomotive and diesel exhaust; aerosols of metalworking (machining) fluids including aldehyde and formaldehyde; aluminum smelter workers exposed to pot-room fumes; metal processing plant workers; pulp mill workers; shoe and leather workers exposed to the organic solvents; workers exposed to SO2 from apricot sulfurization; airborne mineral spirits; SO3 release; cement dust in manufacturing; aldehydes including formaldehyde and glutaraldehyde; biologic dusts and endotoxins; tunnel construction workers; coke oven emissions; cleaning and disinfecting workers in the food industry; welding fumes; chili pepper pickers; cyanoacrylates glues used in large amounts; methyl isocyanate environmental release; airborne fiberglass insulation; dust exposure in Norwegian smelters; spray foam insulation; 2-hydroxyethyl methacrylate and methyl methacrylate in dentists; synthetic leather workers exposed to organic solvents toluene, xylene and methyl ethyl ketone; eucalyptus; fragranced aerosol products; bleach products used by cleaners; metal fumes; irritant gas containing chromate at a chrome pellet manufacturing plant; diesel exhaust exposure; nickel sulfate in electroplating; arsenic trichloride in pharmaceutical & pesticide manufacturing; phosgene; ammonium and NH3 agents; potassium solutions and sodium persulfate inorganic salts used as oxidizing agents in hair bleaches and hair-coloring preparation; gases from liquid manure; additive 2-diethylaminoethanolamine; cleaners using cleaning products in a spray form.|
Table 1: Common causes of irritation.
Instigated irritant exposures activate Transient Receptor Potential (TRP) ion channels that open cationic pores permitting intracellular influx of calcium and sodium ions to initiate the nerve impulse [17-21]. In particular, TRP subfamily A, member 1 (TRPA1) cationic channels located on the plasma membrane of many cells provides the final transduction cog through which irritant agents elicit inflammatory and other changes .
There is poor understanding of the induction of a greater irritant response among some individuals. Genetic factors may impose greater host susceptibility for acute lung injury [23-27]. Glutathione Stransferase P, encoded by the GSTP1 gene, causes more of a burden due to reactive oxygen species [28,29]. Feasibly, there is derangement of airway smooth muscle with faster proliferation of smooth muscle cells and heighten smooth muscle mass among subjects with irritantinduced asthma [30,31].
Irritancy evolves within minutes to hours after an irritant exposure . An irritant provokes reacting tissue to release an array of signaling molecules from an “inflammatory soup” [32-34]. The signaling molecules trigger infiltration of inflammatory cells, vascular congestion and augmented blood flow; there is adjoining edema from leaking plasma as well as glandular hyper secretion and nerve sensitivity . Radiation-induced tissue damage leads to the generation of short-lived free radicals, changes in cellular DNA, and incitement of an inflammatory response containing proinflammatory cytokines, chemokines, receptor tyrosine kinase, and adhesions molecules . Initially, there is rapid proliferation and maturation of basal keratinocytes, hair follicle stem cells and melanocytes. Additional exposure to radiation results in further direct tissue injury, inflammation, and impaired epithelial regeneration.
A rejoinder or response to irritancy may be unpleasant; but, perhaps it is just a warning signal evolved millions of generations ago . Nociception is the sensory nervous system's response to harmful or potentially harmful stimuli propagated by a sub population of nerve fibers. Chemesthesis involves burning, stinging or definite pain; it is typically a response by the skin, eyes, nose and throat. The degree of irritancy is modified, enhanced or diminished by prior exposures or by pre-existing disease. It is not yet determined whether atopic individuals are more likely to note irritancy [37,38]. In a Guinea pig model, irritants bind to ion channels provoking neurogenic inflammation with release of neuropeptides; the small neuronal signaling molecules on cell surfaces liberate inflammatory moieties that signal between populations of neurons [39-41]. Possibly, neuropeptides act as a priming substance to increase vascular permeability related to skin irritancy . A similar response in humans has not yet been definitively established [43,44].
Irritants form complex biological connections through chemical cross-linking reactions, interaction with sulfur or cysteine molecules and creation of double bonds with human proteins [45,46]. Reactive halogenated compounds display varying degrees of carbon atomshalogen substitution. An irritant’s vapor pressure, at normal air temperature, influences the likelihood of a higher air level after an accidental irritant release. Solubility governs irritant’s airway localization, upper vs. lower airway involvement. A more soluble irritant will more likely dissolve in the upper airways’ fluid milieu. The physical interaction between an irritant and a receptor protein embedded in a lipid layer is predictive of a chemical’s potential for sensory irritation . Various determinants of irritancy are available. RD50 refers to the concentration of an irritant causing a 50% decrease in the breathing rate (RD50) of an exposed mouse . Another irritancy predictor is the Quantitative Structure Relationship (QSAR) [49,50].
The most common of the irritant’s effect is sensory annoyance involving different target sites. Prevention of chemical damage to the eye requires wearing tight-fitting protective goggles. Eye irritation manifests as a burning/stinging/pain sensation (chemesthesis), tearing and conjunctival redness. There may be accompanying eyelid swelling and blurred vision. Eye involvement is considered a medical emergency especially after a highly alkaline or extremely acidic chemical agent exposure; the grave risk is for corrosive eye damage that worsens by the minute . In such an emergency, immediately flush the eye with water; continue to rinse for at least 10 minutes . Remove contact lenses. Do not let the patient rub their eyes, even after flushing with water. Therapeutically, antibiotic ointment into the eye may prevent infection while a topical corticosteroid may reduce inflammation. In most cases, chemicals will merely cause eyes’ surface damage and not permanent loss of vision. Subsequent follow-up eye examinations require slit-lamp assessment and, perhaps, a battery of ophthalmologic tests, such as measurement of the time for tear film break-up, adequacy of foam formation in the eye canthus and evidence of conjunctival epithelial damage; there may be additional eye testing parameters [52,53].
The nose, as an irritant target manifests nasal inflammation and mucosal erythema [54,55]. There is rhinorrhea along with swelling and congestion of the nasal mucosa. Excessive nasal fluid can drip down the back of the throat (i.e., post-nasal drip) or escape out from the nostrils. Sneezing happens whenever foreign particles irritate the nasal mucosa . A massive irritant exposure leads to a worse nasal outcome [56-58]. Hyposmia refers to the reduced ability to smell and to detect odors while anosmia is the absolute incapability of detecting odors. Parosmia or troposmia misidentifies a pleasant or neutral odor for an unpleasant odor.
Throat irritation leads to a sore throat often with painful swallowing. There may be a scratchy feeling at the back of the throat or a sensation of a lumpy feeling or something stuck at the back of the throat . Usually, there is an ongoing dry cough. Hoarseness shadows laryngitis . Pharyngeal edema, redness and posterior pharynx drainage are observed on physical examination. Most cases of throat irritation resolve without special treatment. Home remedies for throat irritation include gargling with warm water twice a day, sipping honey with lemon mixture or sucking on medicated lozenges (containing menthol). Additional therapy for difficulty in swallowing includes drinking more fluids and chewing on ice chips.
Skin irritation happens after there are disruptions of the protective skin barrier with subsequent water loss, suppressed epidermal lipid production, pH-dependent susceptibility to infection, inflammation and altered calcium gradients [61,62]. Skin keratinocytes release both inflammatory chemotactic and growth promoting cytokines; also, oxidative stress causes tissue damage [33,42,61].
Spirometric Reductions in FEV1 follow exposures to phenolformaldehyde resins and repeated chlorine gassings [65-71]. Aluminum pot room workers and individual exercising at room and cold temperatures show changes in FEV1 [72,73]. Boilermaker construction working at gas coal and oil-fired plants, exposure of emergency responders to a variety of fumes, gases, and particulates during the course of their job and machinists’ exposures to machining fluids incite FEV1 alterations [74-76]. It is important to stress that performance of performing spirometry necessitates accurate methodology and use of an acceptable spirometer that displays a flowvolume curve [66,77].
Enhanced Airway Response to an Allergen, to which an individual is before hand sensitized, follows inhaling a low level of an environmental irritant air pollutant [85-88]. In atopic subjects, an enhanced response occurs when particulates rather than clean air precedes the allergen challenge . "Enhancement" refers to a greaterthan- additive response after the delivery of an irritating agent to an allergen, compared with the responses when the irritant and allergen delivery occurs by itself.
Elevated Levels of Exhaled Breath Nitric Oxide (FENO) are reported for pulp-mill and bleachery workers sustaining episodes of ozone gassing . Workers with different irritant exposures (i.e., underground workers exposed to particulates and nitrogen dioxide; shoe and leather workers exposed to toluene, xylene and methyl ethyl ketone; and, swine confinement workers) exhibit higher FENO [35,91-93]. Using FENO as a monitoring tool needs careful application .
Induced Sputum examination discerns different cell types, such as epithelial and squamous cell, cancer or atypical cells, neutrophils, macrophages and eosinophils . Irritant-exposures influence neutrophilia rather than eosinophilia [22,96-101]. Higher induced sputum neutrophilia is seen after a diesel exhaust particulate exposure . Testing New York City Firefighters 10 months after the collapse of the World Trade Center, shows more induced sputum neutrophilia in association with a more intense exposure to World Trade Center dust [103,104]. Asthmatic subjects and endurance athletes develop sputum neutrophilia after an ozone challenge [105,106]. Fast food grill kitchen workers exhibit high numbers of alveolar macrophages in induced sputum samples . Bronchoalveolar lavage (BAL) fluid cells in rats following chlorine exposure display an increase in the numbers of neutrophils . Pre-treatment of a one-week course of parenteral steroids dampens neutrophilic inflammation in rats after irritant instillation .
Glutathione conversion to an oxidized form (GSSG) provides less antioxidant protection . An increase in the ratio of the oxidized disulfide form of glutathione (GSSG) in relations to the reduced glutathione configuration (GSH) is indicative of oxidative stress (i.e., GSSG/GSH) . Numerous investigations address glutathione kinetics and oxidative stress after an irritant exposure.
Irritant-induced Asthma-the Beginning
For more than half of the 20th century, there is a primary belief that occupational asthma is an allergy-related disorder, preceded by latency (of months or years), whereby repeat inhalational exposures to one of more than 250 allergenic workplace agents initiate immunologic sensitization, which ultimately leads to workplace-associated asthmatic manifestations . Yet concealed, is a seeming lack of appreciation for the relevancy of irritancy. Cases incriminating irritants seem overlooked perhaps because of limited reporting or a paucity subjects studied [111-114].
History warns about the potential for irritant consequences. In the 1920s, at the start of World War I, German forces fire more than 150 tons of chlorine gas against two French colonial divisions at Ypres, causing serious consequences . By the time World War II ended in 1945, at least 4,000 Service Men participate in experimental exposures using mustard or Lewisite agents in gas chambers or in contaminated field experiments . Surviving veterans report anatomic changes with symptomatic respiratory manifestations [117-120]. Use of mustard gas during the 1980s’ Iran/Iraq War exposes Iranians soldiers who subsequently display persistent Spiro metric reductions . More cases of asthma are noted among Iranian military veterans experiencing heavy mustard gas exposure 10 years before .
Gandevia et al. describe workers with new-onset asthma following exposures to high concentrations of hydrogen sulfide smoke and fumes from overheated plastics. There is reference to “acute inflammatory bronchoconstriction” . Firemen fighting a fire at a polyurethane foam manufacturing factory are exposed to the high concentrations of toluene diisocyanate (TDI) vapors emanating from two large storage tanks damaged during the fire . A majority of firefighters describes acute irritation of their eyes, nose, and throat and some firefighters develop acute tightness of the chest, breathlessness and cough at the scene of the fire. Some firefighters disclose temporary spirometric decline during the first 6 months after the fire. Because TDI is a very common cause of allergic occupational asthma, its irritancy (non-allergy) may not have been fully appreciated. Perhaps, the delay in the recognition of Reactive Airways Dysfunction Syndrome (RADS) and an acute irritant-induced airways disorder is because of RADS’s low prevalence, somewhere less than 20% of workers with the diagnosis of “occupational asthma” [124,125].
Reactive Airways Dysfunction Syndrome (RADS)
In 1985, Brooks and associates coin the acronym "Reactive Airways Dysfunction Syndrome" (RADS) to depict cases of acute, non-allergic, irritant-induced asthma without latency following a high-level inhalation exposure to an irritating gas, vapor or fume. On occasion, RADS is consequential of an airborne aerosol or mist exposure . Rarely if ever, does RADS follow an exposure to massive levels of dust particles.
Typically, the onset of RADS appears within 24-hours, especially when the afflicted person is in close proximity to the irritant’s source of origin [127,128]. When first observing the patient with evolving RADS, he/she is in acute distress with a faster breathing rate (tachypnea) of more than 20 breaths per minute. There may be an accompanying tachycardia with the heart rate greater than 90 beats per minute. Blood pressure and temperature readings vary. Pulse oximetry level is often low or at a low-normal level. It is the health professional’s obligation to determine whether there are physical examination findings depicting eye, nose, throat, and/or skin irritancy. Table 2 provides diagnostic criteria for RADS diagnosis.
|Diagnostic criteria for RADS|
|A documented absence of preceding respiratory complaints manifesting asthma symptomatology, account of past childhood asthma or a history of asthma in remission|
|The onset of symptoms occurred after a single and specific exposure, which was present in very high concentrations and had irritant qualities to its nature|
|Onset of asthma complaints occurred within minutes to hours and always within 24 hours after the exposure.|
|The exposure was to a gas, smoke, fume, or vapor. Rarely, if ever was the exposure to a dust|
|Finding of a positive meth choline challenge test (≤ 8 mg/ml) following the exposure, indicative of non-specific bronchial hyper responsiveness.|
|Pulmonary function tests may show airflow obstruction.|
|Another pulmonary disorder to explain the symptoms and findings was excluded especially conditions that simulated asthma (such as vocal cord dysfunction)|
Table 2: Diagnostic criteria for RADS.
As soon as clinically feasible, procure specific details about the exposure, especially the precise nature of the exposure (i.e., chemical name, physical state, vapor pressure, etc.); and, ask how long it lasted. A critical bit of information is to ascertain whether the exposure is massive in nature. Is the exposure the result of an accidental explosion with the irritant agent release under pressure? How close is the afflicted individual (s) to the exposure source? Does the exposure take place in an open or an enclosed space? Valuable information is contained in the Material Safety Data Sheets (MSDSs) uncovering the precise constituents of the exposure. Typically, the MSDS information discloses the percentage concentration of chemical ingredients and physical properties. Scrutinize whether the chemical exposure comprises a dilute concentration. Is there a fire with the emissions of combustion products (smoke, fumes, and/or gases)?
Various etiologic irritants are presumed for RADS development [127,129-137]. Transiently obstructive airways are unveiled in some of the workers four years after an industrial accident involving a pyrite dust explosion estimated to release between 300 and 1,600 ppm of sulfurous gases . Respiratory symptoms follow a high-level hydrogen sulfide gas exposure from agitation of liquid manure . An individual develops severe airway obstruction after inhaling fumes from a mixture of several drain cleaning agents .
Typically when investigating RADS cases, spirometry shows airflow obstruction . A reduced Tiffeneau-Pinelli index (FEV1/FVC ratio) is an indicator of airflow limitation . Some subjects show ‘normal’ or mild airflow limitation with insignificant bronchodilator response (≤ 12% improvement in FEV1). Infrequently, affected persons exhibit a restrictive lung defect suggestive of a mixed pattern . The latter finding brings suspects for extra thoracic upper airways obstruction, such as with vocal cord dysfunction (VCD) .
Airway Hyperresponsiveness is the hallmark of RADS, usually by documenting a positive methacholine aerosol provocation with PC20 of ≤8 mg/ml. PC20 refers to the provocative conc entration of methacholine causing a 20% fall in FEV1 [142,143]. There may be employment of other methods for identifying hyperresponsive airways [143,144].
RADS’s respiratory symptoms may be transient and resolve within 12 weeks or less . One review of RADS reports a median duration of symptoms lasting 13 months (interquartile range, 6.5 to 43.5 months) . Mostly, individuals with RADS demonstrate continuation of nonspecific airway hyperresponsiveness and chronic asthma-type symptoms .
Lung pathology recognizes denuded bronchial epithelium, polynuclear and mononuclear cellular inflammation (eosinophilia tends to be absent), edematous mucosa, squamous cell metaplasia, basement membrane thickening, collagen proliferation and bronchial wall fibrosis [69,129,146]. There is continuing airway mononuclear inflammation as well as perpetual structural changes, transformed airway remodeling, induced neural plasticity and incessant airway hyperresponsiveness . An investigation involving accidental chlorine gas exposure reports pathological changes of repeat bronchial biopsies taken over a 5-month time-period . Initial denudation of the bronchial epithelial cells accompanies exudative sub mucosal fibrinous hemorrhage. Later, there is epithelial layer proliferation with regeneration of basal and Para basal cells. The latest pathological change divulges collagen deposition. Bronchoepithelial cell injury and lymphocytic inflammation persist when bronchial biopsies are obtained 3 years after an exposure causing RADS [149,150].
Astute clinical scrutiny is a prerequisite for successful management of any serious inhalation injury since the clinical course may change from minute to minute. At the latest, the patient needs examination by a physician within the first 1-2 h after the exposure. Preferably, there is prompt transport of the patient to a hospital’s Emergency Department since it permits accessibility to necessary medical consultative services, the availability of observation and/or hospital treatment in an intensive care unit . Several hours may ensue between the time an exposure occurs and when manifestations that are more critical evolve. It is best to insure an observation period lasting 24-48 h before discharge. With very serious acute lung inhalational injuries, the chest x-ray shows alveolar and/or mixed infiltrates or segmental consolidation . Challenging clinical scenarios include diffuse alveolar envelopment, as with the Adult Respiratory Distress Syndrome (ARDS), disseminated pneumonia with sepsis and shock or massive non-cardiac pulmonary edema. Chest computed tomography will best define lung changes . ARDS, localized pneumonia or non-cardiac heart failure that may accompany RADS requires appropriate management. Aerosolized bronchodilators may be the administration for bronchoconstriction (as measured by spirometry) or for bronchospasm (as determined by auscultation finding of wheezing). The use of inhaled bronchodilator is especially relevant when there is reversibility of airway obstruction. However, reversibility of airway obstruction tends to be less marked in RADS than in asthma [145,154].
Differential diagnosis may be challenging in RADS since the routine chest roentgenogram may appear relatively ‘normal’ in the immediate post-exposure period. As time passes, there may evolve a more hyperinflated X-ray appearance with lower diaphragms. Fiber optic bronchoscopic inspection is considered helpful as a visual gauge of the severity of the airway injury for most, if not all, inhalation injuries, [151,155]. Serial fiber optic examinations objectively assess the extent of the airway injury and the therapeutic benefits; discoveries may necessitate alterations in management . RADS cases show tracheobronchial mucosal erythema and edema. In more severe cases, there is bronchial lining ulceration and/or hemorrhage .
Systemic corticosteroid, in high doses, may provide limited benefit since inflammation is mononuclear rather than eosinophilic. A beneficial effect of parental steroids in a rat model of RADS is of note when dexamethasone administration is immediately before chlorine inhalation . A short course of high dose corticosteroid therapy does not improve the outcomes of patients with ARDS . There is not definitive data on corticosteroid use in RADS involving humans. An antidotal report claims inhaled steroids are beneficial in RADS [145,148].
Meat Wrapper’s Asthma is the result of the meat wrapping procedure (used commonly in the 1970s) involving wrapping packages of meat with polyvinyl chloride (PVC) plastic wrapping film. After meat wrapping, the plastic film is cut from the main PVC roll using a thin wire heated to between 150-200°C; wrap edges are sealed using a hot plate. The labels are also heated. The heating process emits irritating PVC pyrolysis byproducts; an airborne pyrolytic byproduct includes di-2-ethyl-hexyl phthalate (DEHP) . The condition is referred to as meat-wrapper’s asthma . Complaints include eye irritation, chest tightness, cough and sometimes wheezing.
Military Deployment, as a military-related exposure leading to newonset asthma, is a mischaracterization . There is reference to "Iraq/Afghanistan War-Lung Injury". There is rejection for labeling deployment as an exposure since it simply is a time spent in a specific military locale . Yearly, nearly 3,000 US military applicants are disqualified from military service because of asthma . A history of prior childhood asthma becomes important because military recruitment concentrates on the age group at which prior childhood asthmatics achieve “remission;” and, these individuals potentially are poised to relapse from a remission. Microscopic and biochemical changes continue into adulthood [163-173]. There is reporting, by countries other than the USA, of asthma recurrence after childhood asthma among military recruits including New Zealand [174-178]. Asthma among cleaners is the claim for new-onset asthma among domestic cleaning women and janitors from frequent use of bleach and other irritant cleaning agent. Supportive investigations for the asthma relationship among cleaners emanates from: 179-185]. New-onset asthma is linked to job tasks of waxing, wax stripping of floor, spot cleaning of carpets, cleaning tiles and cleaning grout [184,186-189].
Potroom asthma is the occurrence of work-related airway symptoms in association with airflow limitation, airway inflammation and persistent nonspecific airway hyperresponsiveness among workers engaged in the primary smelting of aluminum, and less commonly among smelters and casters of refined aluminum. The entity is referred to as “Potroom asthma” [73,190-194]. Suspicious etiologic factors are particulates of aluminum sodium fluoride along with hydrogen fluoride and other gases [194-199].
Swimming pool use and asthma occur among individuals frequenting public swimming pools that use chlorine as a disinfectant [200-209]. Swimming pool lifeguards with frequent exposure to total chloramine levels report acute eyes and upper airway symptoms but do not show bronchial hyperresponsiveness . The process of disinfection of swimming pools requires generation of ‘free chlorine’ through addition of sodium hypochlorite (liquid bleach), calcium hypochlorite or chlorine gas [205,210]. Public swimming pool water is comprised of organic precursors of the tap water used to fill the pools. Additional swimming pool contaminants are sweat, urine, skin particles, hair, microorganisms, cosmetics, and personal care products .
Athletes Exposed to unconditioned cold air develop exerciseinduced bronchospasm beginning 5-10 minutes of exercise; there is bronchospasm resolution within 30 to 60 minutes after stopping exercise or following a β2-agonist treatment [211,212]. A high prevalence of exercise-induced bronchospasm is of note for collegiate cross-country runners and elite athletes exercising in cold mountain environs . Exercising speed and power athletes may increase their ventilation rate as much as 200 liters per minute for short periods of time . The mechanism to explain exercise-induced bronchospasm suggests that hyperventilation leads either to airway cooling with airway water loss and/or, in some manner, changes the osmolality of periciliary fluid lining evoking mucosal release of endogenous mediators causing airway smooth muscle contraction [214,215]. Being in a cold (and relatively dry) mountain environment produces more rapid respiratory water vapor loss as the exercise ventilatory rate increases. There is also the possibility that strenuous exercise triggers injury to the airway epithelium rather than affecting airway smooth muscle. The ensuing airway epithelial injury-repair process contributes to subsequent bronchial hyperresponsiveness.
Exacerbation of mild or preexisting asthma in remission may be etiologic for some cases of acute irritant-induced asthma. Cases of asthma can achieve a "remission" and/or display a reduction in asthma complaints. However, there remains a risk for future exacerbations of asthma [166-173,216]. Sometimes, an acute asthmatic exacerbation ensues when an individual with mild or controlled asthma experiences an irritant environment trigger. This response is an acute exacerbation of a “preexisting” condition and not “new onset” asthma.
Vocal Cord Dysfunction (VCD)
Asthma is an intrathoracic reversible obstructive airway disorder. In contrast, VCD represents a spectrum of extrathoracic upper airway/ laryngeal obstructive entities [217-220]. VCD mimics an acute asthmatic attack (Table 3) offers clinical clues differing between asthma and VCD. With VCD, there is fleeting obstruction of the upper airways due to inspiratory closure of vocal folds; sometimes closure is also during expiration . Approximately 15% of US-American military recruits with suspected asthma exhibit VCD . Eucalyptus exposure precipitates VCD in a 46-year-old woman . VCD may be provoked by methacholine challenge testing . A 15 year old teen develops VCD while working in a corn field . VCD is of note among elite athletes during sporting competitions ; some competitive swimmers develop VCD . A unique investigation connects VCD to occupancy in water damaged buildings . Finally, VCD is discovered in about 10% of former World Trade Center rescue and recovery workers as well as volunteers involved in the rescue operation . Spirometry shows flattening of the inspiratory loop of the flow-volume curve. Typically during an acute VCD attack, endoscopy reveals 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 a physician’s prescribed medications [230,231]. Phonatory function tests, videostroboscopy and laryngeal image analysis are available tests for VCD [60,232]. With videostroboscopy, a steel scope containing a tiny camera and strobe light is place in the subject’s mouth. The angle of the camera allows a clear and painless view of the patient's glottis and supraglottic regions. There is slow motion videotape assessing of vocal cord movement and vibration by projecting a moving image of the vocal cords, frame by frame, onto the television monitor. Ancillary therapeutic approaches for VCD may require psychological and psychiatric management applying behavioral, psychodynamic and/or pharmacological options . Relaxation training and using biofeedback may be appropriate if marked anxiety and/or panic contribute to VCD symptomatology. Marital and/or family counseling may also be beneficial.
|Affected Site||Intrathoracic||Extra thoracic|
|Onset||Minutes, Hours||Seconds, Sudden|
|Triggers||Allergens, Cold Air, Strenuous Exercise, Mental Stress||Exertion, Cold Air,
|Response to Odorant||No or Occasional||Typical|
|Duration of Attack||Variable, Hours or Days||Short, Seconds to Minutes|
|Dyspnea||During Attacks||Attacks and at Most Times|
|Cough||Episodic, Productive||Persistent, Dry|
|Status Between Attacks||Normal||Complaints|
|Voice||Normal||Hoarseness, Actual Loss|
|Auscultation||Expiratory & Inspiratory Wheezing||Inspiratory Wheezing and Stridor|
|Spirometry||Reduced FEV1/FVC% & Expiratory Airflow Obstruction||Flattening or Truncated Inspiratory Loop of Flow-Volume Curve|
|Endoscopy||Bronchial Mucosal Erythema, Edema and Secretion||Vocal Cord Anterior 2/3 Adduction with Posterior Chinking|
|Role of Eosinophil||Yes & Often||No|
|Aggressive Therapy||May be Effective||Not Effective|
Table 3: Differentiating Asthma and VCD.
Irritant-Associated Vocal Cord Dysfunction is linked to an inhalational exposure declared as being RADS . Eleven individuals who manifest voice change are initially considered to have RADS or asthma because there was a temporal association between onset of respiratory symptom and prior occupational or environmental exposure. All 11 individuals show negative methacholine challenges but laryngoscopic evidence of VCD. Workplace exposures of note are ammonia, flux fumes after inappropriate mixing of flux and solder, aerosolized cleaning chemicals, a specific odor (cooked spicy salmon), organic solvent, aerosolized machining fluid and smoke and ceiling tile dust falling through the ceiling above his workstation engulfing the worker below. The facts about the exposures do not indicate a massive or high-level irritant gas, vapor or fume exposure as necessary for RADS diagnosis. Dust is almost never a cause of RADS. A question regarding this entity is analogous to asking the question: what arose first, the chicken or the egg? A pivotal question is whether VCD is caused by the irritant exposure and was the initial RADS declaration a physician’s failure to correctly gauge the magnitude and toxicological aspects of the suspected/claimed inhalation exposure. The author believes the latter.
Irritable Larynx Syndrome, develops when laryngeal neurons are held in a "spasm-ready" state leading to triggering of symptoms by different extraneous stimuli . Key clinical features of the overreactive laryngeal process comprise muscular tension dysphonia, episodic laryngospasm and cough . Important diagnostic criteria are when there are symptoms attributable to laryngeal tension such as dysphonia, laryngospasm with or without throat complaints and/or chronic cough. There may be evidence of visible and palpable muscular tension in and around the neck and larynx with an abnormal laryngeal posture; there is laryngoscopic evidence of vocal cord contraction and/or palpable muscular tension in and around the larynx with abnormal laryngeal posture. Finally, sensory triggers including perfume, foods, emotion, voice use, esophageal irritants and distinctive odorants produce laryngeal muscle spasm with episodic coughing [234,235]. There may be episodic dyspnea, dysphonia, cough and sensation of tension in the throat. Gastroesophageal reflux disorder (GERD) plays a role in more than 90% of cases with resolution of complaints after effective treatment for GERD . About 1/3rd of cases are considered either psychological or viral illness in origin . As for the latter, in some manner a viral illness will “reset” the sensitivity of the larynx to various stimuli. Additionally, occupational exposures may act as an etiologic trigger in some cases . Of interest is that approximately 10% of work-associated respiratory symptoms are referred to a specialist occupational lung disease clinic in Canada .
VCD among Exercising Athletes is a relatively common findings among those athletes screened for asthma while taking part in the 2004 Olympics . Approximately 8% of the screened athletes suffered from VCD . Many cases of VCD occurred only during exercise, especially among elite or intense-training athletes [238,240,241]. Elite or intense-training athletes as well as swimmers, runners and cold-air athletes are at the greatest risk for VCD development [206,207,242]. Eucapneic voluntary hyperventilation testing can uncover some cases of VCD divided into three categories of supraglottic, glottic and mixed (glottic and supraglottic) upper airway obstruction .
Role of Odors and Inhalation Exposures
It is a wonder how influential smelling an odor can be . Clinical studies suggest enhancement of irritant sensitivity by an odorant [245,246]. Odorant stimuli evoke emotion and stimulate an autonomic state via nervous pathways from the amygdala, prefrontal cortex and hippocampus [247,248]. Olfaction encompasses the chemoreception process prompting the sense of smell . Chemoreception is the unique olfactory way that allows a volatile odorant to institute sensory input to parts of the brain designated for smell identification but also for memory and emotion [247,250]. Categorically, a workplace “smell” does not equate with the presence of a dangerous chemical exposure. There are vast differences between the detection concentration of an airborne odorant perceived by smell and the much higher level of the airborne odorant (by magnitudes) capable of causing pungency, irritation or even significant toxicity [5,251,252].
Pavlovian Sensitization is a mechanistic conditioning process taking place among some individuals who develop panic attacks with dyspnea following smelling an odorant [253-255]. Some individuals mentions exposure to organic solvents as causing panic attacks. Such individuals acquire panic attacks after intravenous sodium lactate challenge; other persons with panic manifestations follow CO2 provocation [8,256].
Aerotoxic Syndrome is recognized by noting a “burning, ”oily- type odor leading to both short- and long-term ill-health effects and, in some cases, respiratory complaints purportedly due to breathing atomized engine oils and/or other chemicals contaminated by recirculated “bleed air” entering airline cabins (Wikipedia, 2017 #6270;Burdon J, 2012 #6271). Most modern aircrafts target a recirculating air system composed of 45% “bleed air” and 55% recirculated air. There is the addition of “bleed air” during flight, after takeoff, shortly before landing and sometimes while on the ground. In actuality, “bleed air” is variable and depends upon the speed of the engine, aircraft design and aircraft types. There is a paucity of reliable and objective information on the subject. Presently, there is an ongoing debate, among different interested parties, as to the actuality of the aerotoxic syndrome. Still, some passengers, pilots and cabin crew believe the addition of contaminated “bleed air” causes headaches, visual difficulties, breathing problems, muscle aching, more tiredness, difficulties concentrating, reduced ability for word finding as well as an inability to adequately focus.
Vocal Cord Dysfunction after an Inhalation Exposure epitomizes acute VCD after smelling an odor or scent presumed to be a toxic exposure . Perchance, VCD misconstrued after noting an actual or presumed odor occurs in a susceptible person who misdirects a stressful experience into a physical manifestation . For the susceptible individual, the perception and attribution of smell is influenced by their less accurate elucidation of the odor . Subjective symptoms occur in response to an odor; other individuals, under the same circumstances, do not . The odor or scent causes acute vocal cord spasm; the individual wishes to “protect” his/her lungs from inhaling a perceived “toxic” constituent. For the susceptible person, odorant-alerting properties of nasal receptors heighten the sensitivity of laryngeal reflexes promulgating VCD [245,246, 259]. A greater number of neural signals pass between the olfactory receptors and the olfactory cortex . Besides enhancement of odor perception to different odorants and innocuous stimuli, there is also voice change and marked resistance to aggressive asthma therapy .
Airway Sensory Hyper reactivity encompasses persons with upper and lower airway complaints and persistent cough with triggering by odorants such as perfumes, flowers, colored paints, cigarette smoke and automobile exhaust fumes . The individuals displays poorer quality of life scores and shows enhanced responsiveness to inhaled aerosols of capsaicin (capsaicin challenge) despite negative methacholine challenge indicative of absent nonspecific airway hyperresponsiveness .
Irritancy reflects a state of being irritated, a condition evolving within minutes to hours. There is impact of irritant exposures in the workplace, public health and community populations. RADS represent an outcome of a massive irritant exposure, manifesting as non-allergic, irritant-induced intrathoracic asthma without latency. The outcome of the very high irritant inhalational exposure causes persistent airway inflammation, perpetual airway structural changes, transformed airway remodeling, induced neural plasticity and incessant airway hyperresponsiveness.
Inexplicably an odor becomes misinterpreted as a more serious consequence, both by patient but enigmatically also by the treating health professional. Besides RADS and clinical associations of irritancy, this manuscript extends examples of presumed irritant exposure incorrectly referenced as an odorous indicator of toxicity. It is important to emphasize that enhanced odorant/scent sensitivity is not a diagnostic criteria for RADS.
Importantly, an irritant-induced condition requires better consideration besides mere focus on a patient’s perception or complaints. Of course, accidents or serious events happen. For inhalational injuries, numerous and divergent parties provide influence and take part in decision-making issues regarding the exposure event and the affected patient. Of course, there is critical participation and input by the treating physician. But, there may also be meetings with family members, conclusions recounted by coworkers, communications by the employer, discussions with public health officials, contact with regulatory agencies, at times, integrating industrial hygiene and/or toxicology information, conceivably deliberating with union representatives, responding to requests made by insurance companies or Workers ’ Compensation officials and possibly hiring an attorney.
Imperatively, when there are health concerns from an inhalational exposure, there is always a physician’s participation. The afflicted patient seeks care from a physician/health care professional for treatment and management of their actual or perceived health issue caused by an inhalational irritant exposure. The concerned patient communicates their account of events and their complaints to a responsive physician/health care professional. The latter is expected to infer a correct diagnosis and recommend proper treatment of an assumed inhalational injury under the circumstances of the described exposure. Regrettably, there may be limitation of training in the intricacies of inhalation injuries and chemical toxicology for some practicing physicians. Analytic features of an inhalation exposure with essentials of chemical reactions, appreciation of acknowledged toxicological doctrines and better grasp of what constitutes a massive exposure may be serious knowledge-gaps of busy practicing physicians. Sometimes, the physician/health care professional’s diagnostic inference is incorrect. Making the correct diagnosis is imperative because of the adverse therapeutic and economic consequences of miss-diagnosing RADS as a serious event. Because the clinical picture simulates RADS or asthma after a reported irritant inhalation exposure, a consulted pulmonary specialist or emergency care provider usually institutes asthma therapy with aerosolized bronchodilators and corticosteroids. The error can lead to repeated Emergency Department visits, continued corticosteroid and bronchodilator administration, possibly multiple hospitalizations and the unwarranted ongoing physician office visits. When the “pieces” of the clinical puzzle do not fit correctly, there must be inclusion of more “pieces” of the clinical picture or rearrangement of “pieces” allowing better scrutiny of the information.
Certainly, because of the notable existence of irritants there is a need for better professional expertise on the subject matter. Because of irritants’ pervasiveness and common consequential health concerns, a better understanding of and preventive strategies for irritant exposures are important. Accordingly, irritantology will be the distinctive knowledge of irritants while an irritantologist holds special expertise in assessing irritants and their health and environmental impacts.
- Wegman DH, Eisen EA (1990) Acute irritants. More than a nuisance. Chest 97: 773–775.
- Blanc PD, Galbo M, Hiatt P, Olson KR (1991) Morbidity following acute irritant inhalation in a population based study. JAMA 266: 664-669.
- Brooks SM (2017) Vocal cord dysfunction after an inhalation exposure. J Allergy Ther 8: 1-8.
- Bell IR, Schwartz GE, Peterson JM, Amend D (1993) Self-reported illness from chemical odors in young adults without clinical syndromes or occupational exposures. Arch Environ Health 48: 6-13.
- Greenberg MI, Curtis JA, Vearrier D (2013) The perception of odor is not a surrogate marker for chemical exposure: A review of factors influencing human odor perception. J Clinical Toxicology 51: 70-76.
- Shim C, Williams MH (1986) Effect of odors in asthma. Am J Med 80: 18-22.
- Poonai NP, Antony MM, Binkley KE, Stenn P, Swinson RP, et al. (2001) Psychological features of subjects with idiopathic environmental intolerance. J Psychosomatic Res 51: 537-541.
- Dager SR, Holland JP, Cowley DS, Dunner DL (1987) Panic disorder precipitated by exposure to organic solvents in the work place. Am J Psychiatry 144: 1056-1058.
- Goh CL (1994) Common industrial processes and occupational irritants and allergens--an update. Ann Acad Med Singapore 23: 690-698.
- Muller WJ, Schaeffer VH (1996) A strategy for the evaluation of sensory and pulmonary irritation due to chemical emissions from indoor sources. J Air Waste Manag Assoc 46: 808-812.
- Occupational Safety and Health Administration (OSHA). The OSHA hazard communication standard (hcs) 1994.
- Brooks SM, Hammad Y, Richards I, Giovinco-Barbas J, Jenkins K (1998) The spectrum of irritant-induced asthma: Sudden and not-so-sudden onset and the role of allergy. Chest 113: 42-49.
- Bray FN, Simmons BJ, Wolfson AH, Nouri K (2016) Acute and chronic cutaneous reactions to ionizing radiation therapy. Dermatol Ther (Heidelb) 6: 185-206.
- Brooks SM (2014) Irritant-induced asthma and reactive airways dysfunction syndrome (RADS). J Allergy Ther 5: 1-7.
- Wisnewski AV, Srivastava A, Herick C, Xu L, Lemus R, et al. (2000) Identification of human lung and skin protein congugated with hexamethylene diisocyanate in vitro and in vivo. Am J Respir Cell Mol Biol 162: 2330-2336.
- Beach JR (2000) Immunologic versus toxicologic mechanisms in airway responses. Occup Med 15: 455-470.
- Taylor-Clark TE, McAlexander MA, Nassenstein C, Sheardown SA, Wilson S, et al. (2008) Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal. J Physiol 586: 3447-3459.
- Martinac B (2004) Mechanosensitive ion channels: Molecules of mechanotransduction. J Cell Sci 117: 2449-2460.
- Huang CL (2004) The Transient Receptor Potential superfamily of ion channels. J Am Soc Nephrol 15: 1690-1699.
- Groneberg DA, Nowak D, Wussow A, Fischer A (2006) Chronic cough due to occupational factors. J Occup Med Toxicol 1: 1-10.
- Brooks SM (2008) Irritant-induced chronic cough: A TRPpathy. Lung 186: S88-S93.
- Bautista DM, Jordt S-E, Nikai T, Tsuruda PR, Read AJ, et al. (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124: 1269-1282.
- Leikauf GD, McDowell SA, Wesselkamper SC, Hardie WD, Leikauf JE, et al. (2002) Acute lung injury. Functional genomics and genetic susceptibility. Chest 121: 70S-75S.
- Reddy AJ, Kleeberger SR (2009) Genetic polymorphisms associated with acute lung injury. Pharmacogenomics 10: 1527–1539.
- Zhai R, Gong MN, Zhou W, Thompson TB, Kraft P, et al. (2007) Genotypes and haplotypes of the VEGF gene are associated with higher mortality and lower vegf plasma levels in patients with ARDS. Thorax 62: 718–722.
- Lesur I, Textoris J, Loriod B, Courbon C, Garcia S, et al. (2010) Gene expression profiles characterize inflammation stages in the acute lung injury in mice. PLoS ONE 5: 1-14.
- Kelly FJ (2003) Oxidative stress: Its role in air pollution and adverse health effects. Occup Environ Med 60: 612-616.
- Mapp CE, Fryer AA, De Marzo N, Pozzato V, Padoan M et al. (2002) Glutathione S-Transferase GSTP1 is a susceptibility gene for occupational asthma induced by isocyanates. J Allergy Clin Immunol 109: 867-872.
- Fryer AA, Bianco A, Hepple M, Jones PW (2000) Polymorphism at the Glutathione S-Transferase GSTP1 locus. A new marker for bronchial hyperresponsiveness and asthma. Am J Respir Crit Care Med 161: 1437–1442.
- Borger P, Tamm M, Black JL MR (2006) Asthma: Is it due to an abnormal airway smooth musclwe cell? Am J Respir Crit Care Med 174: 367-372.
- Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, et al. (2008) Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 178: 218-224.
- Barnes PJ (1992) Neurogenic inflammation and asthma. J Asthma 29: 165-180.
- Lee HY, Stieger M, Yawalkar N, Kakeda M (2013) Cytokines and chemokines in irritant contact dermatitis. Mediators Inflamm 2013: 1-7.
- Zhang N, Oppenheim JJ (2005) Cross talk between cytokines and neuronal receptors bridge immune and nervous system. J Leuko Biol 78: 1210-1214.
- Demnati R, Fraser R, Plaa G, Malo J (1995) Histopathological effects of acute exposure to chlorine gas on sprague-dawley rat lungs. J Environ Pathol Toxicol Oncol 14: 15-19.
- Clark TT, Undem BJ (2006) Transduction mechanisms in airway sensory nerves. J Appl Physiol 101: 950-959.
- Shusterman D (1994) Neurogenic inflammation: Additional points. Environ Health Perspect 102: 12-13.
- Morris JB, Symanowicz PT, Olsen JE, Thrall RS, Cloutier MM, et al. (2003) Immediate sensory nerve-mediated respiratory responses to irritants in healthy and allergic airway-diseased mice. J Appl Physiol 94: 1563-1571.
- Canning BJ (2006) Anatomy and neurophysiology of the cough reflex: ACCP evidence-based clinical practice guidelines. Chest 129: 33-47.
- Mazzone SB (2004) Sensory regulation of the cough reflex. Pulm Pharmacol Ther 17: 361-368.
- Widdicombe JG (2003) Overview of neural pathways in allergy and asthma. Pulm Pharmacol Ther 16: 23-30.
- Gutwald J, Goebeler M, Sorg C (1991) Neuropeptides enhance irritant and allergic contact dermatitis. J Invest Dermatol 96: 695-698.
- Canning BJ, Farmer DG, Mori N (2006) Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs. Am J Physiol Regul Integr Comp Physiol 291: 454-463.
- Groneberg DA, Quarcoo D, Frossard N, Fischer A (2004) Neurogenic mechanisms in bronchial inflammatory diseases. Allergy 59: 1139-1152.
- Jarvis J, Seed MJ, Elton R, Sawyer L, Agius R, et al. (2005) Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds. Occup Environ Med 62: 243-250.
- Abraham MH, Hassanisadi M, Jalali-Heravi M, Ghafourian T, Cain WS, et al. (2003) Draize rabbit eye test compatibility with eye irritation thresholds in humans: A quantitative structure-activity relationship analysis. Toxicol Sci 76: 384-391.
- Nielsen GD, Alarie Y (1982) Sensory irritation, pulmonary irritation, and respiratory stimulation by airborne benzene and alkylbenzenes: Prediction of safe industrial exposure levels and correlation with their thermodynamic properties. Toxicol Appl Pharmacol 65: 459-477.
- Alarie Y (1973) Sensory irritation by airborne chemicals. Crit Rev Toxicol 3: 299-363.
- Tong W, Hong H, Xie Q, Shi L, Fang H, et al. (2005) Assessing qsar limitations–a regulatory perspective. Current Computer-Aided Drug Design 1: 195-205.
- Hayashia M, Nakamuraa Y, Higashia K, Kato H, Kishida F, et al. (1999) A quantitative structure–activity relationship study of the skin irritation potential of phenols. Toxicol In Vitro 13: 915-922.
- Kjaergaard S, Pedersen OF, Mølhave L (1992) Sensitivity of the eyes to airborne irritant stimuli: Influence of individual characteristics. Arch Environ Health 47: 45-50.
- Gorguner M, Akgun M (2010) Acute inhalation injury. Eurasian J Med 42: 28-35.
- Pan Z, Mølhave L, SK K (2000) Effects on eyes and nose in humans after experimental exposure to airborne office dust. Indoor Air 10: 237-245.
- Koren HS, Devlin RB (1992) Human upper respiratory tract responses to inhaled pollutants with emphasis on nasal lavage. Ann N Y Acad Sci 641: 215-224.
- Shusterman D (2011) The effects of air pollution and irritants on the upper airway. Proc Am Thorac Soc 8: 101-105.
- Castano R, Malo JL (2010) Occupational rhinitis and asthma: Where do we stand, where do we go? Curr Allergy Asthma Rep 10: 135-142.
- Meggs WV, Cleveland C, Metzger WJ, Larkin E, Albernaz M (1992) Reactive upper-airway dysfunction syndrome (ruds): A form of irritant rhinitis induced by chemical exposure. J Allergy Clin Immunol 89: 170.
- Meggs WJ (1994) RADS and RUDS--the toxic induction of asthma and rhinitis. J Toxicol Clin Toxicol 32: 487-501.
- Cometto-Muniz JE, Cain WS (1992) Sensory irritation. Relation to indoor air pollution. Ann N Y Acad Sci 641: 137-151.
- Yumoto E (2004) Aerodynamics, voice quality, and laryngeal image analysis of normal and pathologic voices. Curr Opin Otolaryngol Head Neck Surg 12: 166-173.
- Eberting CL (2014) Irritant contact dermatitis: Mechanisms to repair. J Clin Exp Dermatol Res 5: 1-8.
- Chew AL, Maibach HI (2003) Occupational issues of irritant contact dermatitis. Int Arch Occup Environ Health 76: 339-346.
- O'Connell PJ, Wang X, Leon-Ponte M, Griffiths C, Pingle SC, et al. (2006) A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells. Blood 107: 1010-1017.
- Van Rijt LS, Lambrecht BN (2005) Dendritic cells in asthma: A function beyond sensitization. Clin Exp Allergy 35: 1125-1134.
- Kennedy SM, Enarson DA, Janssen RG, Chan-Yeung M (1991) Lung Health Consequences of Repeated Accidental Chlorine Gas Exposures among Pulpmill Workers. Am Rev Respir Dis 143: 74-79.
- Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, et al. (2005) Ats/ers task force: Standardisation of spirometry. Eur Respir J 26: 319-338.
- Mathur N, Rastogi SK (2007) Respiratory effects due to occupational exposure to formaldehyde: Systematic review with meta-analysis. Indian J Occup Environ Med 11: 26-31.
- Leroyer C, Malo JL, Infante-Rivard C, Dufour JG, Gautrin D (1998) Changes in airway function and bronchial responsiveness after acute occupational exposure to chlorine leading to treatment in a first aid unit. Occup Environ Med 55: 356-359.
- Gautrin D, Leroyer C, L'Archeveque J, Dufour JG, Girard D, et al. (1995) Cross-sectional assessment of workers with repeated exposure to chlorine over a three year period. Eur Respir J 8: 2046-2054.
- Maghni K, Lemiere C, Ghezzo H, Yuquan W, Malo JL (2004) Airway inflammation after cessation of exposure to agents causing occupational asthma. Am J Respir Crit Care Med 169: 367-372.
- Bherer L, Cushman R, Courteau Jp, Quevillon M, Cote G, et al. (1994) Survey of construction workers repeatedly exposed to chlorine over a three to six month period in a pulpmill: Ii. Follow up of affected workers by questionnaire, spirometry, and assessment of bronchial responsiveness 18 to 24 months after exposure ended. Occup Environ Med 51: 225-228.
- Evans TM, Rundell KW, Beck KC, Levine AM, Baumann JM (2005) Airway narrowing measured by spirometry and impulse oscillometry following room temperature and cold temperature exercise. Chest 128: 2412-2419.
- Desjardins A, Bergeron JP, Ghezzo H, Cartier A, Malo JL (1994) Aluminium potroom asthma confirmed by monitoring of forced expiratory volume in one second. Am J Respir Crit Care Med 150: 1714-1717.
- Hauser R, Eisen EA, Pothier L, Lewis D, Bledsoe T, et al. (2002) Spirometric abnormalities associated with chronic bronchitis, asthma, and airway hyperresponsiveness among boilermaker construction workers. Chest 121: 2052-2060.
- Kennedy SM, Chan-Yeung M, Teschke K, Karlen B (1999) Change in airway responsiveness among apprentices exposed to metalworking fluids. Am J Respir Crit Care Med 159: 87-93.
- McCluskey JD, Harbison SC, Johnson GT, Xu P, Morris S, et al. (2014) Occupational health surveillance: Pulmonary function testing in emergency responders. J Emerg Trauma Shock 7: 180-185.
- Brusasco V, Crapo R, Viegi G (2005) Ats/ers task force: Standardisation of lung function testing. Eur J Respir Dis 26: 319-338.
- Gueders MM, Foidart JM, Noel A, Cataldo DD (2006) Matrix metalloproteinases (mmps) and tissue inhibitors of mmps in the respiratory tract: Potential implications in asthma and other lung diseases. Eur J Pharmacol 533: 133-144.
- Atkinson JJ, Senior RM (2003) Matrix metalloproteinase-9 in lung remodeling. Am J Respir Cell Mol Biol 28: 12-24.
- Brooks SM (2011) Irritant induced airways disorders. Immunol Allergy Clin North Am 31: 747-768.
- Malo JL, L’Archeveˆque J, Castellanos L, Lavoie K, Ghezzo H, et al. (2009) Long-term outcomes of acute irritant-induced asthma. Am J Respir Crit Care Med 179: 923-928.
- Gordon SB, Curran A, Fishwick D, Morice AH, Howard P (1998) Respiratory symptoms among glass bottle workers--cough and airways irritancy syndrome? Occup Med (Lond) 48: 455-459.
- Greaves IA, Eisen EA, Smith TJ, Pothier LJ, Kriebel D, et al. (1997) Respiratory health of automobile workers exposed to metal-working fluid aerosols: Respiratory symptoms. Am J Ind Med 32: 450-459.
- Maghni K, Malo JL, L'Archevêque J, Castellanos L, Gautrin D (2010) Matrix metalloproteinases, il-8 and glutathione in the prognosis of workers exposed to chlorine. Allergy 65: 722-730.
- Jorres R, Nowak D, Magnussen H (1996) The effect of ozone exposure on allergen responsiveness in subjects with asthma or rhinitis. Am J Respir Crit Care Med 153: 56-64.
- Lange DS, Jorres RA, Mucke M, Siegfried W, Magnussen H (1998) Interactions between human bronchialepithelial cells and lung fibroblasts after ozone exposure in vitro. Toxicol Lett 97: 13-24.
- Peden DB, Boehlecke B, Horstman D, Devlin R (1997) Prolonged acute exposure to 0.16 ppm ozone induces eosinophilic airway inflammation in asthmatic subjects with allergies. J Allergy Clin Immunol 100: 802-808.
- Davies RJ, Wang J, Abdelaziz MM, Calderon MA, Khair O, et al. (1997) New insights into the understanding of asthma. Chest 111.
- Hauser R, Rice TM, Murthy GGM, Wand MP, Lewis D, et al. (2003) The upper airway response to pollen is enhanced by exposure to combustion particulates: A pilot human experimental challenge study. Environ Health Perspect 111: 472-477.
- Olin AC, Ljungkvist G, Bake B, Hagberg S, Henriksson L, et al. (1999) Exhaled nitric oxide among pulpmill workers reporting gassing incidents involving ozone and chlorine dioxide. Eur Respir J 14: 828-831.
- Ulvestad B, Bakke B, Eduard W, Kongerud J, Lund MB, et al. (2001) Cumulative exposure to dust causes accelerated decline in lung function in tunnel workers. Occupational & Environmental Medicine 58: 663-669.
- Ulvestad B, Lund MB, Bakke B, Djupesland PG, Kongerud J, et al. (2001) Gas and dust exposure in underground construction is associated with signs of airway inflammation. Eur Respir J 17: 416-421.
- Maniscalco M, Grieco L, Galdi A, Lundberg JO, Sofia M, et al. (2004) Increase in exhaled nitric oxide in shoe and leather workers at the end of the work-shift. Occup Med (Lond) 54: 404-407.
- Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, et al. ( 2011) American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. An official ATS clinical practice guideline:Interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 184: 602-15.
- Pavord ID, Pizzichini MM, Pizzichini E, Hargreave FE (1997) The use of induced sputum to investigate airway inflammation. Thorax 52: 498-501.
- Lee LY, Widdicombe JG (2001) Modulation of airway sensitivity to inhaled irritants: Role of inflammatory mediators. Environ Health Perspect 109: 585-589.
- Cohn LA, Adler KB (1992) Interactions between airway epithelium and mediators of inflammation. Exp Lung Res 18: 299-322.
- Fahy JV (2009) Eosinophilic and neutrophilic inflammation in asthma Insights from clinical studies. Proc Am Thorac Soc 6: 256-259.
- Zhang Y, Goss AM, Cohen ED, Kadzik R, Lepore JJ, et al. (2008) A GATA6-WNT pathway required for epithelial stem cell development and airway regeneration. Nat Genet 40: 862-870.
- Beghe B, Padoan M, Moss CT, Barton SJ, Holloway JW, et al. (2004) Lack of association of hla class I genes and TNF alpha-308 polymorphism in toluene diisocyanate-induced asthma. Allergy 59: 61-64.
- Levitt J, Matthay MA (2010) The utility of clinical predictors of acute lung injury: Towards prevention and earlier recognition. Expert Rev Respir Med 4: 785-797.
- Nightingale JA, Maggs R, Cullinan P, Donnelly LE, Rogers DF, et al. (2000) Airway inflammation after controlled exposure to diesel exhaust particulates. Am J Respir Crit Care Med 162: 161-166.
- Fireman EM, Lerman Y, Ganor E GJ, Fireman-Shoresh S, Lioy PJ, et al. (2004) Induced sputum assessment in New York City firefighters exposed to World Trade Center dust. Environ Health Perspect 112: 1564-1569.
- Skoner DP, Doyle WJ, Seroky J, Van Deusen MA, Fireman P (1996). Lower airway responses to Rhinovirus 39 in healthy allergic and nonallergic subjects. Eur Respir J 9: 1402-1406.
- Nightingale JA, Rogers DF, Barnes PJ (1999) Effect of inhaled ozone on exhaled nitric oxide, pulmonary function, and induced sputum in normal and asthmatic subjects. Thorax 54: 1061-1069.
- Bonsignore MR, Morici G, Vignola AM, Riccobono L, Bonanno A, et al. (2003) Increased airway inflammatory cells in endurance athletes: What do they mean? Clin Exp Allergy 33: 14-21.
- Sivertsen I, Sjaastad AK, Svendsen K, Krokje A (2002) Alveolar macrophages as biomarkers of pulmonary irritation in kitchen workers. Ann Occup Hyg 46: 713-717.
- Demnati R, Fraser R, Ghezzo H, Martin Jg, Plaa G, et al. (1998) Time-course of functional and pathological changes after a single high acute inhalation of chlorine in rats. Eur Respir J 11: 922-928.
- Rahman I (2005) Regulation of glutathione in inflammation and chronic lung diseases. Mutat Res 579: 58-80
- Malo JL, Yeung MC (2001) Occupational asthma. Journal of Allergy and Clinical Immunology 108: 317-328.
- Charan N, Meyer C, Lakshminarayan S, Spencer T (1979) Pulmonary injuries associated with acute sufur dioxide inhalation. Am Rev Respir Dis 119: 555-560.
- Kowitz T, Reba R, Parker R, Spicer W (1967) Effects of chlorine gas upon respiratory function. Arch Environ Health 14: 545-558.
- Hasan FM, Gehshan A, Fuleihan FJ (1983) Resolution of pulmonary dysfunction following acute chlorine exposures. Arch Environ Health 38: 76-80.
- Banks DE (2001) Workplace irritant exposures: Do they produce true occupational asthma? Curr Opin Allergy Clin Immunol 1: 163-168.
- Germans introduce poison gas, 2010.
- Dickerson C (2015) Secret world war II chemical experiments tested troops by race.World war II secret mustard gas testing. NPR, Public Radio, Washington DC, USA.
- Veress LA, O’Neill HC, Hendry-Hofer TB, Loader JE, Rancourt RC, et al. (2010) Airway obstruction due to bronchial vascular injury after sulfur mustard analog inhalation. Am J Respir Crit Care Med 182: 1352-1361.
- Ghanei M, Tazelaar HD, Chilosi M, Harandi AA, Peyman M, et al. (2008) An international collaborative pathologic study of surgical lung biopsies from mustard gas-exposed patients. Respir Med 102: 825-830.
- Khateri S, Ghanei M, Keshavarz S, Soroush M, Haines D (2003) Incidence of lung, eye, and skin lesions as late complications in 34,000 Iranians with wartime exposure to mustard agent. J Occup Environ Med 45: 1136-1143.
- Consensus Study Report (1993) Committee on the Survey of the Health Effects of Mustard Gas and Lewisite. Veterans at risk: The health effects of mustard gas and Lewisite. Institute of Medicine, Washington DC, USA.
- Emad A, Rezaian GR (1997) The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: Analysis of 197 cases. Chest 112: 734-738.
- Gandevia B (1970) Occupational asthma. Med J Aust 2: 332-335.
- Axford AT, McKerrow CB, Jones AP, Le Quesne PM (1976) Accidental exposure to isocyanate fumes on a group of firemen. Br J Ind Med 33: 65-71.
- Nemery B (1996) Late consequences of accidental exposure to inhaled irritants: RADS and the Bhopal disaster. Eur Respir J 9: 1973-1976.
- Chatkin JM, Tarlo SM, Liss G, Banks D, Broder I (1999) The outcome of asthma related to workplace irritant exposures: A comparison of irritant-induced asthma and irritant aggravation of asthma. Chest 116: 1780-1785.
- McDonald JC, Chen Y, Zekveld C, Cherry NM (2005) Incidence by occupation and industry of acute work related respiratory diseases in the UK, 1992-2001. Occup Environ Med 62: 836-842.
- Kern DG (1991) Outbreak of the reactive airways dysfunction syndrome after a spill of glacial acetic acid. Am Rev Respir Dis 144: 1058-1064.
- Johnsen HL, Hetland SM, Saltyte BJ, Kongerud J, Soyseth V (2008) Quantitative and qualitative assessment of exposure among employees in Norwegian smelters. Ann Occup Hyg 52: 623-633.
- Brooks SM, Weiss MA, Bernstein IL (1985) Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures. Chest 88: 376-384.
- Gautrin D, Bernstein IL, Brooks SM (2006) Reactive airways dysfunction syndrome, or irritant induced asthma. Asthma in the workplace.
- Henneberger PK, Derk SJ, Davis L, Tumpowsky C, Reilly MJ, et al. (2003) Work-related reactive airways dysfunction syndrome cases from surveillance in selected US states. J Occup Environ Med 45: 360-368.
- Malo JL (1998) Irritant-induced asthma and reactive airways dysfunction syndrome. Can Respir J 5: 66-67.
- Donham K, Knapp L, Monson R, Gustafson K (1982) Acute toxic exposure to gases from liquid manure. J Occup Med 24: 142-145.
- Flury KE, Dines DE, Rodarte JR, Rodgers R (1989) Airway obstruction due to ammonia. Mayo Clinic Proc 58: 389-393.
- Lemiere C, Malo JL, Gautrin D (1996) Nonsensitizing causes of occupational asthma. Med Clin North Am 80: 749-774.
- Shakeri MS, Dick FD, Ayres JG (2008) Which agents cause reactive airways dysfunction syndrome (RADS)? A systematic review. Occup Med 58: 205-211.
- Tarlo SM, Broder I (1989) Irritant-induced occupational asthma. Chest 96: 297-300.
- Härkönen H, Nordman H, Korhonen O, Winblad I (1983) Long-term effect from exposure to sulfur dioxide: Lung function four years after a pyrite dust explosion. Am Rev Repir Dis 128: 840-847.
- Murphy D, Fairman R, Lapp NL (1976) Severe airways disease due to the inhalation of fumes from cleaning agents. Chest 69: 372-376.
- Swanney MP, Ruppel G, Enright PL, Pedersen OF, Crapo RO, et al. (2008) Using the lower limit of normal for the fev1/fvc ratio reduces the misclassification of airway obstruction. Thorax 63: 1046-1105.
- Ciccolella DE, Brennan KJ, Borbely B (1997) Identification of vocal cord dysfunction (VCD) and other diagnoses in patients admitted to an inner city university. Am J Respir Crit Care Med 155: 82.
- Brooks SM, Bernstein I, Raghuprasad PK, Maccia CA, Mieczkowski L, et al. (1990) Assessment of airway hyperresponsiveness in chronic stable asthma. J Allergy Clin Immunol 85: 17-36.
- Crapo RO, Casaburi R, Coates AL,Enright PL,Hankinson JL, et al. (2000) Official Statement by the American Thoracic Society. Guidelines for methacholine and exercise challenge testing-1999. Am J Respir Crit Care Med 161: 309-329.
- Banks DE, Tarlo SM, Masri F, Rando RJ, Weissman DN, et al. (1996) Bronchoprovocation tests in the diagnosis of isocyanate-induced asthma. Chest 109: 1370-1379.
- Malo JL, L’Archeveque J, Castellanos L, Lavoie K, Ghezzo H, et al. (2009) Long-term outcomes of acute irritant-induced asthma. Am J Respir Crit Care Med 179: 923-928.
- Bernstein IL, Bernstein DI (1989) Reactive airways dysfunction syndrome (RADS) after exposure to toxic ammonia fumes. J Allergy Clin Immunol 83: 173-179.
- Brooks SM, IL B (1999) Reactive airways dysfunction syndrome or irritant induce asthma. Asthma in the workplace New York: Marcel Dekker Publisher 565-593.
- Lemiere C, Malo Jl,Boutet M (1997) Reactive airways dysfunction syndrome due to chlorine: Sequential bronchial biopsies and functional assessment. Eur Respir J 10: 241-244 .
- Deschamps D, Rosenberg N, Soler P, Maillard G, Fournier E, et al. (1992) Persistent asthma after accidental exposure to ethylene oxide. Br J Ind Med 49: 523-525.
- Deschamps D, Soler P, Rosenberg N, Baud F, Gervais P, et al. (1994) Persistent asthma after inhalation of a mixture of sodium hypochlorite and hydrochloric acid. Chest 105:1895-1896.
- Dries DJ, Endorf FW (2013) Inhalation injury: epidemiology, pathology, treatment strategies. Scan J Trauma Resusc Emerg Med 21: 31-46.
- Miller K, Chang A (2003) Acute inhalation injury. Emerg Med Clin N Am 21: 533-557.
- Desai SR, Wells AU, Suntharalingam G, Rubens MB, Evans TW, et al. (2001) Acute respiratory distress syndrome caused by pulmonary and extrapulmonary injury: A comparative ct study. Radiology 218: 689-693.
- Gautrin D, Boulet LP, Boutet M, Dugas M, Bhérer L, et al. (1994) Is reactive airways dysfunction syndrome a variant of occupational asthma?. J Allergy Clin Immunol 93: 12-22.
- Heimbach DM, Waeckerle JF (1988) Inhalation injuries. Ann Emerg Med 17: 1316-1320.
- Moylan JA, Chan C-K (1978) Inhalation injury-an increasing problem. Ann Surg 188: 34-37.
- Demnati R, Fraser R, Martin Jg, Plaa G, Malo Jl, et al. (1998) Effects of dexamethasone on functional and pathological changes in rat bronchi caused by high acute exposure to chlorine. Toxicol Sci 45: 242-246.
- Hough CL (2014) Should we ever give steroids to ards patients?. Clin Chest Med 35: 781-795.
- Brooks SM, Vandervort RJ (1977) Polivinyl chloride film thermal descomposition products as an occupational illness. J Ocupp Med 19: 192-198.
- Szema AM (2013) Occupational lung diseases among soldiers deployed to Iraq and Afghanistan. Occup Med Health Aff 1: 1-23.
- Falvo MJ, Bradley M, Brooks SM (2014) Is deployment an "exposure" in military personnel?. J Occup Environ Med 56: 139-140.
- Martin BL, Engler RJM, Klote MM, With CM, Krauss MR, et al. (2006) Asthma and its implications for military recruits. In: Martha K. Lenhart MD P, Borden Institute, editor. Recruit Medicine. Walter Reed Army Medical Center, Washington, DC Office of The Surgeon General at TMM Publications 2006.
- Kelly WJ, Hudson I, Phelan PD, Pain MC, Olinsky A (1987) Childhood asthma in adult life: A further study at 28 years of age. Brit Med J 294: 1059-1062.
- Oswald H, Phelan PD, Lanigan A, Hibbert M, Bowes G, et al. (1994) Outcome of childhood asthma in mid-adult life. brit Med J 309: 95-96.
- Sears MR, Greene JM, Willan AR, Wiecek EM, Taylor DR, et al. (2003) A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med 349: 1414-1422.
- Amin K, Ludviksdottir D, Janson C, Nettelbladt E, Roomans G, et al. (2000) Inflammation and structural changes in the airways of patients with atopic and nonatopic asthma. Am J Respir Crit Care Med 162: 2295-2301.
- Clark NM, Dodge JA, Thomas LJ, Andridge RA, Awad D, et al. (2010) Asthma in 10 to 13 year olds: Challenges at a time of transition. Clin Pediatr (Phila) 49: 931-937.
- Riiser A, Hovland V, Carlsen KH, Mowinckel P, Carlsen KCL (2012) Does bronchial hyperresponsiveness in childhood predicts active asthma in adolescence?. Am J Respi Crit Care Med 86: 493–500.
- Roorda RJ, Gerritsen J, van Aalderen WMC, Schouten JP, Veltman JC, et al. (1994) Follow−up of asthma from childhood to adulthood: Influence of potential childhood risk factors on the outcome of pulmonary function and bronchial responsiveness in adulthood. J Allergy Clin Immunol 93: 575-584.
- Ségala C, Priol G, Soussan D, Liard R, Neukirch F, et al. (2000) Asthma in adults: Comparison of adult-onset asthma with childhood-onset asthma relapsing in adulthood. Allergy 55: 634-640.
- Taylor DR, Cowan JO, Greene JM, Willan AR, Sears MR (2005) Asthma in remission. Can relapse in early adulthood be predicted at 18 years of age?. Chest 127: 845-850.
- Toorn VDLM, Overbeek SE, Jongste DJC, Leman K, Hoogsteden HC, et al. (2001) Airway inflammation is present during clinical remission of atopic asthma. Am J Respir Crit Care Med 164: 2107-2113.
- Williams HE, McNicol KN (1975) The spectrum of asthma in children. Pediatr Clin North Am 22: 43-52.
- Bronnimann S, Burrows B (1986) A prospective study of the natural history of asthma. Remission and relapse rates. Chest 90: 480-484.
- Dickinson JG (1988) Asthma in the army: A retrospective study and review of the natural history of asthma and its implications for recruitment. JR Army Med Corps 134: 65-74.
- Adams R, Wilson D, Appleton S, Taylor A, Dal G, et al. (2003) Underdiagnosed asthma in south australia. Thorax 58: 846–850.
- Katz I, Moshe S, Sosna J, Baum G, Fink G, et al. (1999) The occurrence, recrudescence, and worsening of asthma in a population of young adults. Impact of varying types of occupation. Chest 116: 614-618.
- Lindström I, Koponen P, Luukkonen R, Pallasaho P, Kauppi P, et al. (2009) Military service-aggravated asthma improves at two-year follow-up. Respiratory Medicine 103: 1926-1935.
- Jaakkola MS, Suuronen K, Luukkonen R, Järvelä M, Tuomi T, et al. (2009) Respiratory symptoms and conditions related to occupational exposures in machine shops. Scand J Work Environ Health 35: 64-73.
- Kopferschmitt-Kubler MC, Ameille J, Popin E, Calastreng-Crinquand A, Vervloet D, et al. (2002) Occupational asthma in France: A 1-yr report of the observatoire national de asthmes professionnels project. European Respiratory Journal 19: 84-89.
- Ng TP, Lee HS, Lee FY, Wang YT, Tay VL, et al. (1991) Occupational asthma due to ethylene diamine. Ann Acad Med Singapore 20: 399-402.
- Buck RG, Miles AJ, Ehrlich RI (2000) Possible occupational asthma among adults presenting with acute asthma. S Afr Med J 90: 884-888.
- Vizcaya D, Mirabelli MC, Antó JM, Orriols R, Burgos F, et al. (2011) A workforce-based study of occupational exposures and asthma symptoms in cleaning workers. Occup Environ Med 68: 914-919.
- Obadia M, Liss GM, Lou W, Purdham J, Tarlo SM. (2009) Relationships between asthma and work exposures among non-domestic cleaners in Ontario. Am J Ind Med 52: 716-723.
- Rosenman KD, Reilly MJ, Schill DP, Valiante D, Flattery J, et al. (2003) Cleaning products and work-related asthma. J Occup Environ Med 45: 556-563.
- Sastre J, Madero MF, Fernández-Nieto M, Sastre B, del Pozo V, et al. (2011) Airway response to chlorine inhalation (bleach) among cleaning workers with and without bronchial hyperresponsiveness. Am J Ind Med 54: 293-299.
- Mirabelli MC, Zock JP, Plana E, Antó JM, Benke G, et al. (2007) Occupational risk factors for asthma among nurses and related healthcare professionals in an international study. Occup Environ Med 64: 474-479.
- Kogevinas M, Zock JP, Jarvis D, Kromhout H, Lillienberg L, et al. (2007) Exposure to substances in the workplace and new-onset asthma: An international prospective population-based study (ECRHS-II) Lancet 370: 336-341.
- Zock JP, Vizcaya D, Le Moual N (2010) Update on asthma and cleaners. Curr Opin Allergy Clin Immunol 10: 114-120.
- Arnaiz NO, Kaufman JD, Daroowalla FM, Quigley S, Farin F, et al. (2003) Genetic factors and asthma in aluminum smelter workers. Arch Environ Health 58: 197-200.
- Lund MB, Oksne PI, Hamre R, Kongerud J (2000) Increased nitric oxide in exhaled air: An early marker of asthma in non-smoking aluminium potroom workers? Occup Environ Med 57: 274-278.
- Sjaheim T, Halstensen TS, Lund MB, Bjortuft O, Drablos PA, et al. (2004) Airway inflammation in aluminium potroom asthma. Occup Environ Med 61: 779-785.
- Soyseth V, Kongerud J, Ekstrand J, Boe J (1994) Relation between exposure to fluoride and bronchial responsiveness in aluminium potroom workers with work-related asthma-like symptoms. Thorax 49: 984-989.
- Van Rooy FGBGJ, Houba R, Stigter H, Zaat VAC, Zengeni MM, et al. (2011) A cross-sectional study of exposures, lung function and respiratory symptoms among aluminium cast-house workers. Occup Environ Med 68: 876-882.
- Kongerud J, Boe J, Soyseth V, Naalsund A, Magnus P (1994) Aluminium potroom asthma: The norwegian experience. Eur Respir J 7: 165-172.
- Lie AEW (1981) Influence of fluoride recovery alumin on the work environment and the health of aluminum potroom workers. Med Lav 7: 214-222.
- Seixas NS, Cohen M, Zevenbergen B, Cotey M, Carter S, et al. (2000) Urinary fluoride as an exposure index in aluminum smelting. Aihaj 61: 89-94.
- Sorgdrager B, de Looff AJ, de Monchy JG, Pal TM, Dubois AE, et al. (1998) Occurrence of occupational asthma in aluminum potroom workers in relation to preventive measures. Int Arch Occup Environ Health 71: 53-59.
- Steinegger AF, Schlatter C (1992) Evaluation of fluoride exposure in aluminium smelters: State of the art. Med Lav 83: 489-498.
- Agabiti N AC, Forastiere F, Di Napoli, A Lo Presti E (2001) Short term respiratory effects of acute exposure to chlorine due to a swimming pool accident. Occup Environ Med 58: 399-404.
- Bar-Or O, Inbar O (1992) Swimming and asthma. Benefits and deleterious effects. Sports Med 14: 397-405.
- Bernard A, Nickmilder M, Voisin C, Sardella A (2009) Impact of chlorinated swimming pool attendance on the respiratory health of adolescents. Pediatrics 124: 1110-1118.
- 203.Li J, Blatchley ER III (2007) Volatile disinfection byproduct formation resulting from chlorination of organic-nitrogen precursors in swimming pools. Environ Sci Technol 41: 6732-6739.
- Massin N, Bohadana AB, Wild P, Hery M, Toamain JP, et al. (1998) Respiratory symptoms and bronchial responsiveness in lifeguards exposed to nitrogen trichloride in indoor swimming pools. Occup Environ Med 55: 258-263.
- Nemery B, Nowak HD (2002) Indoor swimming pools, water chlorination and respiratory health. Eur Respir J 19: 790-793.
- Thickett KM, McCoach JS, Gerber JM, Sadhra S, Burge PS (2002) Occupational asthma caused by chloramines in indoor swimming-pool air. Eur Respir J 19: 827-832.
- Bougault V, Turmel J, St-Laurent J, Bertrand M, Boulet LP (2009) Asthma, airway inflammation and epithelial damage in swimmers and cold-air athletes. Eur Respir J 33: 740-746.
- Wanivenhaus F, Fox AJS, Chaudhury S, Rodeo SA (2012) Epidemiology of injuries and prevention strategies in competitive swimmers. Sports Health 4: 246-251.
- Bernard A, Carbonnelle S, Dumont X, Nickmilder M (2007) Infant swimming practice, pulmonary epithelium integrity, and the risk of allergic and respiratory diseases later in childhood. Pediatrics 119: 1095–1103.
- Weisel CP, Richardson SD, Nemery B, Aggazzotti G, Baraldi E (2009) Childhood asthma and environmental exposures at swimming pools: State of the science and research recommendations. Environ Health Perspect 117: 500-507.
- Anderson SD (2011) Exercise-induced bronchoconstriction in the 21st century. J Am Osteopath Assoc 111: S3-S10.
- McFadden ER (1995) Exercise-induced airway obstruction. Clin Chest Med 16: 671-682.
- Haahtela T, Malmberg P, Moreira A (2008) Mechanisms of asthma in Olympic athletes--practical implications. Allergy 63: 685-694.
- McFadden ER (1994) Gilbert IA. Exercise-induced asthma. New Engl J Med 330: 1362-1367.
- Weiss P (2011) Exercise-induced bronchoconstriction in children and adolescents. J Asthma Allergy Educ 2: 246-252.
- Panhuysen CIM, Vonk JM, Koeter GH, Schouten JP, Van Altena R, et al. (1997) Adult patients may outgrow their asthma. A 25-year follow-up study. Am J Respir Crit Care Med 155: 1267-1272.
- Dunn NM, Katial RK, Hoyle FCL (2015) Vocal cord dysfunction: A review. Asthma Res Pract 1: 1-8.
- Brugman S (2003) The many faces of vocal cord dysfunction. What 36 years of literature tells us. Am J Respir Crit Care Med 167: A588.
- Bahrainwala AH, Simon MR (2001) Wheezing and vocal cord dysfunction mimicking asthma. Curr Opin Pulm Med 7: 8-13.
- Truong A, Truong D-T (2011) Vocal cord dysfunction:An updated review. Otolaryngol 1: 2.
- Morris MJ, Oleszewski RT, Sterner JB, Allan PF (2013) Vocal cord dysfunction related to combat deployment. Mil Med178: 1208-1213.
- Huggins JT, Kaplan A, Martin-Harris B, Sahn SA (2004) Eucalyptus as a specific irritant causing vocal cord dysfunction. Ann Allergy Asthma Immunol 93: 299-303.
- Perkins PJ, Morris MJ (2002) Vocal cord dysfunction induced by methacholine challenge test. Chest 122: 1988-1993.
- Weinberger M, Doshi D (2017) Vocal cord dysfunction: A functional cause of respiratory distress. Breathe 13: 15-21.
- McFadden ER, Zawadski DK (1996) Vocal cord dysfunction masquerading as exercise-induced asthma. A physiologic cause for "choking" during athletic activities. Am J Respir Crit Care Med 153: 942-947.
- Wilson JJ, Theis SM, Wilson EM (2009) Evaluation and management of vocal cord dysfunction in the athlete. Current Sports Medicine Reports 8: 65-70.
- Cummings KJ, Fink JN, Vasudev M, Piacitelli C, Kreiss K (2013) Vocal cord dysfunction related to water-damaged buildings. J Allergy Clin Immunol Pract 1: 46-50.
- De la Hoz RE, Shohet MR, Bienenfeld LA, Afilaka AA, Levin SM, et al. (2008) Vocal cord dysfunction in former World Trade Center (WTC) rescue and recovery workers and volunteers. Am J Ind Med 51: 161-165.
- Newman KB, Mason III UG, Schmaling KB (1995) Clinical features of vocal cord dysfunction Am J Respir Crit Care Med 152: 1382-1386.
- Patel RR, Venediktov R, Schooling T, Wang B (2015) Evidence-based systematic review: Effects of speech-language pathology treatment for individuals with paradocical vocal fold motion. Am J Speech Lang Pathol 24: 566-584.
- Newman KB, Dubester SN (1995) Vocal cord dysfunction: Masquerader of asthma. Respir Crit Care Med 15.
- Hertegård S (2005) What have we learned about laryngeal physiology from high-speed digital videoendoscopy? Curr Opin Otolaryngol Head Neck Surg 13: 152-156.
- Perkner JJ, Fennelly KP, Balkissoon R, Bartelson BB, Ruttenber AJ, et al. (1998) Irritant-associated vocal cord dysfunction. J Occup Environ Med 40: 136-143.
- Morrison M, Rammage L, Emami AJ (1999) The irritable larynx syndrome. J Voice 13: 447-455.
- Morice AH, Fontana GA, Sovijarvi AR, Pistolesi M, Chung KF, et al. (2004) The diagnosis and management of chronic cough. Eur Respir J 24: 481-492.
- Rolla G, Colagrande P, Magnano M, Debernardi V, Dutto L, et al. (1998) Extrathoracic airway dysfunction in cough associated with gastroesophageal reflux. J Allergy Clin Immunol 10 2: 204-209.
- Hoy RF, Ribeiro M, Anderson J, Tarlo SM (2010) Work-associated irritable larynx syndrome. Occup Med 60: 546–551.
- Bussotti M, Di Marco S, Marchese G (2014) Respiratory disorders in endurance athletes – how much do they really have to endure? Open Access J Sports Med 5: 47-62.
- Nascimento T, Gershon T (2013) The psychological experience of athletes with vocal cord dysfunction. J Clin Sport Psychol 7: 146-160.
- Rundell KW, Slee JB (2008) Exercise and other indirect challenges to demonstrate asthma or exercise-induced bronchoconstriction in athletes. J Allergy Clin Immunol 122: 238-246.
- Newsham KR, Klaben BK, Miller VJ, Saunders JE (2002) Paradoxical vocal-cord dysfunction: Management in athletes. J Athl Train 37: 325-328.
- Thole RT, Sallis R, Rubin A, Smith G (2001) Exercise-induced bronchospasm prevalence in collegiate cross-country runners. Med Sci Sports Exerc 33: 1641-1646.
- Turmel J, Gagnon S, Bernier M, Boulet LP (2015) Eucapnic voluntary hyperpnoea and exercise-induced vocal cord dysfunction. BMJ Open Sport Exerc Med 1: e000065.
- Shusterman D (2002) Review of the upper airway, including olfaction, as mediator of symptoms. Environ Health Perspect 4: 649-653.
- Kobal G, Hummel T (1998) Olfactory and intranasal trigeminal event-related potentials in anosmic patients. Laryngoscope 108: 1033-1035.
- Rombaux P, Mouraux A, Bertrand B, Guerit JM, Hummel T, et al. (2006) Assessment of olfactory and trigeminal function using chemosensory event-related potentials. Neurophysiol Clin 36: 53-62.
- Kadohisa M (2013) Effects of odor on emotion, with implications. Front Syst Neurosci 10: 1-6.
- McEwen BS (2007) Physiology and neurobiology of stress and adaptation: Central role of the brain. Physiol Rev 87: 873-904.
- Desesa CR, Vaughan RP, Lanosa MJ, Fontaine KG, Morris JB, et al. (2008) Sulfur-containing malodorant vapors enhance responsiveness to the sensory irritant capsaicin. Toxicol Sci 104: 198-209.
- Emsenhuber B (2011) The olfactory medium Science. Technol Innov Studies 7: 47-64.
- Herz RS (2009) Aromatherapy facts and fictions: A scientific analysis of olfactory effects on mood, physiology and behavior. Int J Neurosci 119: 263-290.
- Shusterman D (2002) Individual factors in nasal chemesthesis. Chem Senses 27: 551-564.
- Rescorla RA (1988) Pavlovian conditioning-it's not what you think it is. Am Psychol 43: 151-160.
- Shusterman D, Balmes J, Cone J (1988) Behavioral sensitization to irritants/odorants after acute overexposures. J Occup Med 30: 565-567.
- Van den Bergh O, Stegen K, Van Diest I, Raes C, Stulens P, et al. (1999) Acquisition and extinction of somatic symptoms in response to odours: A Pavlovian paradigm relevant to multiple chemical sensitivity. Occup Environ Med 56: 295-301.
- Poonai N, Antony MM, Binkley KE, Stenn P, Swinson RP, et al. (2000) Carbon dioxide inhalation challenges in idiopathic environmental intolerance. J Allergy Clin Immunol 105: 358-363.
- Shorter E (1992) From paralysis to fatigue: A history of psychosomatic illness in the modern era. New York: The Free Press.
- Smeets MAM (2005) Evaluating the human response to chemical: Odor, irritation and non--sensory factors. Environ Toxicol Pharmacol 19: 581-588.
- Rex MAE (1970) A review of the structural and functional basis of laryngospasm and a discussion of the nerve pathways involved in the reflex and its clinical significance in man and animals. Br J Anaesth 42: 891-899.
- Homma I, Onimaru HYF (2010) Respiratory response toward olfactory stimuli might be an index for odor-induced emotion and recognition. New Frontiers in Respiratory Control Advances in Experimental Medicine and Biology. New York, NY: Springer.
- Ternesten-Hasseus E, Farbrot A, Lowhagen O, Millqvist E (2002) Sensitivity to methacholine and capsaicin in patients with unclear respiratory symptoms. Allergy 57: 501-507.
- Ternesten-Hasseus E, Lowhagen O, Millqvist E (2007) Quality of life and capsaicin sensitivity in patients with airway symptoms induced by chemicals and scents: A longitudinal study. Environ Health Perspect 115: 425-429.
- Kenn K, Hess MM (2008) Vocal cord dysfunction. An important differential diagnosis of bronchial asthma. Dtsch Arztebl Int 105: 699-700.
Citation: Brooks SM (2018) Irritants, Irritancy and Irritant Induced Asthma. J Allergy Ther 9: 273. DOI: 10.4172/2155-6121.1000273
Copyright: © 2018 Brooks SM. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Select your language of interest to view the total content in your interested language
Share This Article
- Total views: 1151
- [From(publication date): 0-2018 - Dec 17, 2018]
- Breakdown by view type
- HTML page views: 1083
- PDF downloads: 68