กลุ่มอาการทางเดินหายใจตอบสนองผิดปกติ หอบหืดจากสารก่อระคายเคือง และยาฆ่าแมลง

Reactive airways dysfunction syndrome (RADS) , Irritant Induced Asthma (IIA) and Pesticides

- แนวทางการวินิจฉัยโรคเหล่านี้ และสาเหตุการเกิดโรค

Reactive airways dysfunction syndrome (RADS) 

Reactive airways dysfunction syndrome (RADS) is defined as the sudden onset of asthma-like symptoms following high-level exposure to a corrosive gas, vapor, or fumes. The term RADS was originally described by Brooks and Lockers in 1981 1 as nonimmunological asthma resulting from exposure to an irritant gas. Given that most cases are recognized retrospectively, often with considerable delay, they usually lack accurate assessment of the exposure intensity and objective evidence of prior normal bronchial hyper-responsiveness required for the diagnosis of RADS.2

The symptoms usually manifest within 24 hours of exposure as bronchitis, with ocular or mucus membrane irritation of the upper airway (depending on the agent) and often require emergency treatment. The presentation of RADS is different from that of true occupational asthma, because it is an acute single event without a significant latency period. Many cases occurred after the 9/11 collapse of the New York World Trade Center, resulting from the inhalation of fumes and particulate matter.3 The American College of Chest Physicians consensus criteria for the diagnosis of RADS were agreed in 1995,4and were:

• Documented absence of preceding respiratory complaint

• Onset after single exposure incident/accident

• Exposure to very high concentration of gas, smoke, fumes, or vapors with irritant properties

• Onset of symptoms within 24 hours after exposure with persistence for at least 3 months

• Symptoms that simulate asthma with cough, wheeze, and dyspnea

• Presence of airflow obstruction on pulmonary function ± nonspecific bronchial hyper-responsiveness

• All other pulmonary disease excluded.

These criteria have been criticized for being overly restrictive by Alberts and do Pico.5 The pathology of RADS shows nonspecific inflammation, with a cellular infiltrate which is primarily lymphocytic with epithelial desquamation.6 Alberts and Brooks describe the “big bang” mechanism of epithelial injury, with activation of nonadrenergic and noncholinergic fibers via axon reflexes giving rise to neurogenic inflammation, macrophage activation, and mast cell degranulation.7 The resulting proinflammatory state, with toxic mediators, gives rise to epithelial injury. Although most people recover, extensive inflammation and epithelial sloughing could reduce receptor thresholds for severe ongoing bronchial hyper-reactivity. To date, there are no animal models of this disease. The literature suggests that RADS should be recognized as a unique form of asthma with significant upper airway symptoms that are often ignored but appear to be part of the condition.8 There is a growing list of recognized causal agents,9which include:

• Household exposure: floor sealants, spray paint, bleaching agents, household cleaners containing morpholine.

• Chemical: chlorine, sulphuric acid, ammonia, hydrochloric acid, acetic acid, phosgene, hydrogen sulphide, sodium azide, sodium hypochlorite, toluene di-isocyanates, organic solvents.

• Industry: paint spraying, metal-coat removers, welding, heated plastics or acids, epoxy resins, perfumes, pesticides, enzymes, industrial cleaning products, dust or molds in silos.

• Other: Fire and smoke inhalation, burning paint fumes, tear gas, locomotive exhaust, World Trade Center collapse in New York.

  
  
  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196486/
  
  

Pesticide Exposure and Airways

The respiratory tract is routinely exposed to low-molecular-weight chemicals and to a variety of many environmental chemical allergens whose inhalation is a leading cause of respiratory diseases, including asthma.^[1] The increased pesticide exposure from occupational, environmental or residential usages over the past three decades may have contributed to the higher incidence of asthma, particularly in children from urban areas.^[2,3]

Development of allergic respiratory diseases requires sensitization, which may be triggered by dermal or respiratory exposure to the sensitizing chemical.^[4] Airways are also exposed to irritants which are noncorrosive chemicals that cause a reversible inflammatory change of the bronchial mucosa.^[5•]Exposure to either sensitizing or irritant chemicals in the workplace may lead to work-related asthma, a recent term that encompasses both occupational asthma (e.g. asthma induced by sensitizer or irritant work exposures) and work-exacerbated asthma, that is pre-existing or concurrent asthma worsened by work factors, including irritant exposures.^[6] When occupational asthma appears after exposure to an inhaled irritant at work, it is termed irritant-induced occupational asthma.^[6]

Reactive airways dysfunction syndrome (RADS) can be considered a subset of irritant-induced asthma (IIA) that develops after an unintentional short-term high-level exposure to nonimmunogenic, highly irritating volatile substances. Pesticides are among the most common agents producing RADS.^[7] Some of the clinical manifestations are very similar to those of asthma (e.g. inflammation, hyper-responsiveness and reversibility of the bronchial constriction), although this syndrome does not involve immunological mechanisms.^[8] The pathomorphologic bronchial biopsies usually show neutrophilic and lymphocytic infiltrations without eosinophilia and some evidence of subepithelial thickening, fibrosis and destruction of the bronchial epithelium.^[9] These histopathological findings are partially reversible and not sufficiently distinctive to be helpful in diagnosis.^[10,11]

Exposures to pesticides may cause a wide range of acute or chronic (long-term) health effects, depending on the toxicity of the pesticide and the level of exposure. The biological activity of a pesticide is determined by its active ingredient that is usually formulated with other chemical compounds to improve its physico-chemical properties. Among these chemicals, organic solvents are also relevant to the final toxicity of the commercial formulation. Table 1 shows the most common pesticides and their mode of action and acute toxicity.

Lungs may be exposed to pesticides by inhalation of solid or liquid aerosols (powders, airborne droplets) and vapors. When commercial formulations of pesticides enter into contact with skin and mucous membranes (eyes, nose, airways), a local irritative or inflammatory reaction may appear depending on their physicochemical characteristics. Although the main health risk occurs during mixing/loading of the concentrated formulation, inhalation of aerosols of diluted pesticides during their spraying also possesses risks. In addition, many pesticides give off a vapor when exposed to air; hence, temperature has a major influence on their volatilization rate, mainly through its effect on the vapor pressure. Thus, higher volatility pesticides (i.e. soil fumigants) pose a greater risk for exposure, particularly in enclosed spaces and near application sites.^[12]

Most of pesticide poisonings from occupational origin occur through skin contact, followed by the combination of respiratory and cutaneous–mucous exposure (41 and 20% of cases, respectively) causing topical effects in the form of dermatitis or skin irritation.^[13•] In contrast, systemic effects occur away from the original point of contact as a result of the pesticide being absorbed into and distributed throughout the body. Thus, respiratory toxicity (bronchoconstriction, bronchorrhea and wheeze) may occur after cutaneous absorption of anticholinesterase pesticides such as organophosphates and methylcarbamates. More uncommonly, it is possible that the dermal absorbed fraction of the herbicide paraquat may be selectively taken up by the lungs in which it may interact with and damage the alveolar–capillary membrane leading eventually to death.^[14]

Several types of pesticides such as organophosphates, chlorophenoxy acid and methylcarbamates have a high risk of causing bronchial asthma-like diseases when they diffuse into the ambient air. However, many diffused pesticides have weak or minimal immunogenicity on the basis of the slight immunomodulatory changes observed in some human immune laboratory parameters.^[15] The subtle immune alterations associated with intermittent and low-dose pesticide exposure do not necessarily evolve into significant health risk (namely, asthma) to the exposed individuals.

http://www.medscape.com/viewarticle/738955_2