Bronchial hyperreactivity

Inhaled steroids (commonly used are beclomethasone, budesonide, triamcinolone, fluticasone, flunisolide) appear to attenuate the inflammatory response, to reduce bronchial hyperreactivity, to decrease exacerbations and to improve health status they may also reduce the risk of myocar dial infar ction, but they do not modify the longterm decline in lung function. Whether- steroids affect mortality remains unclear. Many patients appear to be resistant to steroids and large, long-term trials have shown only limited effectiveness of inhaled corticosteroid ther apy. Certainly, the benefit from steroids is smaller in COPD than in asthma. Topical side-effects of inhaled steroids are oropharyngeal candidiasis and hoarse voice. At the normal doses systemic side-effects of inhaled steroids have not been firmly established. The current recommendation is that the addition of inhaled gluco-coiticosteroids to bronchodilator treatment is appropriate for patients with severe to veiy sever e COPD. 

Empey, D.W., Laitinen, L.A., Jacobs. L., Gold, W.M. and Nadel, J.A. (1976). Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection. Am. Rev. Resp. Dis. 113, 131 - 139. 

Yeadon, M. and Payne, A.N. (1989). Ozone-induced bronchial hyperreactivity to histamine and ovalbumin in sensitised guinea-p differences between intravenous and aerosol challenge. Eur. Resp. J. 2, 2995. 

Yeadon, M., Wilkinson, D., Darley-Usmar, V., O Leary, V.J. and Payne, A.N. (1992). Mechanisms contributing to ozone-induced bronchial hyperreactivity in guinea-pigs. Pulmon. Pharmacol. 5, 39-50. 

Yeadon, M., Eve, D. and Payne, A.N. (1993b). Ozone exposure in guinea-pigs induces bronchial hyperreactivity to histamine and salbutamol, but not to leukotriene D4. Br. J. Pharmacol. 108, 220P. 

Campbell EM, Charo IF, Kunkel SL, et al. Monocyte chemoattractant protein-1 mediates cockroach allergen-induced bronchial hyperreactivity in normal but not CCR2 / mice the role of mast cells. J Immunol 1999 163(4) 2160-2167. 

McGraw DW, Forbes SL, Kramer LA et al. Transgenic overexpression of beta[2]-adrenergic receptors in airway smooth muscle alters myocyte function and ablates bronchial hyperreactivity. J Biol Chem 1999 274 32241-32247. 

If disease is mediated by non-specific activation of the alternative pathway, it does not explain why some mill workers, who are presumably exposed to equal dust levels, do not develop symptoms. One possible explanation is that there is host factor variability, such as end-organ sensitivity. It has also been proposed that pre-existing, non-specific bronchial hyperreactivity may be Important in development of byssinosis (51), but, to date, there is little evidence for this hypothesis (52- ). 

Studies of GPCRs in asthma can be differentiated on the basis of whether they measure the contribution of candidate genes to atopy, bronchial hyperreactivity (BHR), drug response/nonresponse, or another phenotype. The contribution of selected GPCR variants to the risk for developing asthma or altered drug response is reviewed. 

Drugs that inhibit allergic inflammma-tory mechanisms or reduce bronchial hyperreactivity, viz., glucocorticoids,... 

After removal from exposure, some patients have had resolution of symptoms. The early detection of TDI-induced occupational asthma and the prompt removal of sensitized workers from exposure may increase the chances of remission. " However, there is evidence from several studies that individuals with TDI-induced asthma may continue to have symptoms of dyspnea and wheezing and bronchial hyperreactivity for 2 or more years after cessation of exposure. In one study, patients with TDI-induced asthma who continued to have exposure to TDI for 2 more years had, as a rule, marked abnormal decreases in spirometric parameters and increases in nonspecific hyperreactivity. In another study, 6 of 12 workers with a convincing history of TDI-... 

Belin L, Wass U, Audunsson G, et al Amines Possible causative agents in the development of bronchial hyperreactivity in workers manufacturing polyurethanes from isocyanates. BrJ Ind Med 40 251-257, 1983... 

Burge P Nonspecific bronchial hyperreactivity in workers exposed to toluene diisocyanate, diphenylmethane diisocyanate and colophony. Eur J Respir Dis 63(suppl 123) 91-96, 1982... 

Methacholine is used to identify bronchial hyperreactivity in patients without clinically apparent asthma. For this indication, the drug is administered by inhalation, and patients who may be developing asthma usually produce an exaggerated airway contraction. Upon completion of the test, a rapid-acting bronchodilator (e.g., inhaled p-adrenoceptor agonist) can be given to counter the bronchoconstrictor effect of methacholine and relieve the patient s discomfort. 

Histamine has only minor uses in clinical medicine. In the past it was used to diagnose pernicious anemia, in which histamine fails to evoke the usual secretion of gastric acid. Histamine has been used to assess bronchial hyperreactivity, although this test may be quite hazardous for asthmatics. Today the main clinical use of histamine is as a positive control injection for allergy skin testing. 

Cromolyn sodium and nedocromil sodium attenuate bronchospasm induced by various stimuli, including antigen, exercise, cold dry air, and sulfur dioxide. They suppress inflammatory cell influx and chemotactic activity along with antigen-induced bronchial hyperreactivity. Also inhibited is C-flber sensory nerve activation in animal models, which may in turn suppress reflex-induced bronchospasm. 

Bronchodilators are helpful in individuals with cough and bronchoconstriction due to bronchial hyperreactivity. They help by improving the effectiveness of cough in clearing secretions. 

In pulmonary function laboratories, histamine aerosol has been used as a provocative test of bronchial hyperreactivity. Histamine has no other current clinical applications. 

The tendency to develop bronchospasm on encountering stimuli that do not affect healthy nonasthmatic airways is characteristic of asthma and is sometimes called "nonspecific bronchial hyperreactivity" to distinguish it from bronchial responsiveness to specific... 

The efficacy of subcutaneous SIT has been clearly shown in a metaanalysis of 43 double-blind placebo-controlled trials in allergic rhinitis as well as another meta-analysis of 16 double-blind placebo-controlled studies in asthma patients [13]. The mean clinical improvement was 45% reduction in symptoms and medication compared with placebo in rhinitis and 40% in asthma patients, which exceeds the effects of drug therapy. A recent meta-analysis also confirmed that asthma responds favorably to SIT [14], However, recently it could also be demonstrated that SIT is effective in patients with house dust mite allergy, allergic rhinitis and asthma [15]. Immunotherapy in these patients not only reduced rhinitis and asthma symptoms as well as rescue medication, but also had an impact on bronchial hyperreactivity over the 3-year follow-up period. 

Pichler CE, Helbling A, Pichler WJ Three years of specific immunotherapy with house-dust-mite extracts in patients with rhinitis and asthma Significant improvement of allergen-specific parameters and of nonspecific bronchial hyperreactivity. Allergy 2001 56 301-306. 

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