Hypersensitive airways

It is also evident that inhaled particles and irritants, such as ozone and SO2, can cause perturbations in both the lungs and the cardiovascular system that can potentially contribute to the increased morbidity and mortality observed with increasing levels of these pollutants. There is httle doubt that these neural responses to inhaled irritants and antigen are increased in persons with hypersensitive airways, pulmonary congestion, and heart disease. Clearly, the roles of these irritants and allergens on these vital pulmonary and cardiovascular functions as well as the mechanisms whereby they defend the body or compromise its function need further delineation. This will help provide the needed mechanistic links between inhaled irritants and increased morbidity and mortality. In addition, it will lead to the identification of target sites for prophylactic and therapeutic intervention. 

Asthma is an extremely complex condition characterized by variable and reversible airways obstmction combiaed with nonspecific bronchial hypersensitivity (1 3). The cause of asthma, which is not always readily diagnosed (4), remains unknown. Days, if not weeks, ate needed to document the spontaneous reversal of the airways obstmction ia some patients. Asthmatics experience both an immediate hypersensitivity response and a delayed late-phase reaction, each mediated by a different pathway. Chronic asthma has come to be viewed as an inflammatory disease (5). The late-phase reaction plays a key role ia iaduciag and maintaining the inflammatory state which ia turn is thought to iaduce the bronchial hyperresponsiveness (6). The airways obstmction results from both contraction of airways smooth muscle and excessive bronchial edema. Edema, a characteristic of inflammatory states, is accompanied, ia this case, by the formation of a viscous mucus which can completely block the small airways. 

Experimental methods for determining the potential of materials to produce hypersensitivity reactions by inhalation use procedures to detect hyperreactivity of the airways as demonstrated by marked changes in resistance to air flow, and the detection of antibodies in blood semm (93). 

The term refers to a distinct clinical syndrome characterized by aggressive and continuous inflammatory disease of the airways with chronic eosinophilic rhinosinus-itis, asthma and often nasal polyposis [6-8]. Aspirin and other NSAIDs that inhibit COX-1 exacerbate the condition, precipitating violent asthmatics attacks. This is a hallmark of the syndrome. The prevalence of aspirin hypersensitivity in the general population ranges from 0.6 to 2.5%, but is much more frequent in adult asthmatic subjects where it reaches 10-15%, although it is often underdiagnosed. 

The answer is c. (Hardman, pp 233—235.) The chief danger of therapy with p-adrenergie blocking agents, such as nadolol and propranolol, is associated with the blockade itself, p-adrenergic blockade results in an increase in airway resistance that can be fatal in asthmatic patients. Hypersensitivity reactions such as rash, fever, and purpura are rare and necessitate discontinuation of therapy... 

In sensitized asthmatic individuals, antigen challenge generally causes a Type I (IgE-mediated) immediate hypersensitivity response by release of preformed mediators, including histamine, and prostaglandins, which are responsible for bronchoconstric-tion and increased vascular permeability. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hyper-secretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is driven by leukotrienes, chemokines and cytokines synthesized by activated mast cells and Th2 cells. Both proteins and haptens have been associated with these types of reactions. 

Griffiths-Johnson, D.A. and Karol, M.H., Validation of a non-invasive technique to assess development of airway hyperreactivity in an animal model of immunologic pulmonary hypersensitivity, Toxicology, 65, 283, 1991. 

Atopic dermatitis has been proposed to be the cutaneous manifestation of IgE-mediated hypersensitive reaction to allergenic substances [29]. Conceptually, antagonizing IgE emerges as a logical therapeutic option. Systemic treatment with omalizumab, however, appears to be less efficacious in the skin than in the airway mucosa [23]. It is possible that small molecule Syk inhibitors may offer a more suitable mode to reach and prevent activation of sensitized dermal mast cells and dendritic cells. 

The importance of PAF in airway hypersensitivity has been confirmed by the protective effect exerted by BN 52021 and related ginkgolides [192] in (i) PAF-induced bronchoconstriction and airway hyperreactivity in both humans and animals (ii) various models of immune anaphylaxis and airway hyperreactivity in animals and, as we shall discuss later (iii) antigen-induced bronchial provocation tests in asthmatic patients. 

Inflamed limg tissue (hypersensitivity pneumonitis, HP), complete obliteration of a large proportion of the airways (severe BO), and damage to the air sacs (emphysema) will reduce the DLco measurement. 

There are other ways in which endotoxins may act to produce cotton dust induced airway disease. These include 1) an instrinsic toxicity due to lipid A, responsible for both pyro-genicity and tissue damage 2) a hypersensitivity reaction involving anti-lipid A antibodies. Further, changes in mechanical properties of the lung could be explained by the release of histamine or serotonin caused by endotoxins. 

Oxymorphone Hypersensitivity to morphine analogs acute asthma attack severe respiratory depression or upper airway obstruction paralytic ileus pulmonary edema secondary to a chemical respiratory irritant. 

Bronchospasm occurs in more than half of the more severe hypersensitivity reactions, either on its own or as an accompaniment to other changes. It is more common, as one would expect, in asthmatic patients and in patients receiving muscle relaxants (where tracheal intubation may be a factor). It should, however, only be regarded as indicative of a reaction if other forms of airway obstruction and other causes of tracheal irritation have been excluded. 

WARNING Long-acting -agonists may T risk of asthma-related death Uses COPD maint Action LA -agonist, relaxes airway smooth muscles Dose 15 meg neb bid, 30 meg/d max Caution [C, ] w/ CV Dz, X- Contra Not for acute asthma component hypersensitivity peds w/ phenothiazines Disp Meg neb SE Chest/back pain, D, sinusitis, leg cramps, dyspnea, rash, flu-synd, T BP, arrhythmias, heart block EMS Monitor ECG for arrhythmias, heart block, and hypokalemia (flattened T waves) T risk of acute asthma attack, treat w/ short-acting [3-agonist OD May cause CP, palpitations, muscle tremors and cramps, and syncope symptomatic and supportive... 

Upper airway injury, pneumonitis wifli massive exposure Ocular, upper and lower inflammation, asflima, hypersensitivity pneumonitis... 

Baur X, Dexheimer E Hypersensitivity pneumonitis concomitant with acute airway obstruction after exposure to hay dust. Respiration 1984 46 354-361. 

The irritant properties of chlorine have been documented in studies with healthy human volunteers as well as in individuals with airway hypersensitivity (Table 22.2). 

Respiratory sensitizer means a substance that induces hypersensitivity of the airways following inhalation of the substance ... 

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