Practical issues in the management of hypersensitivity reactions: sulfonamides.

Approximately 3% of the general population and 60% of patients with human immunodeficiency virus (HIV) infection have adverse reactions when treated with sulfonamide antimicrobials. The most common clinical manifestations of sulfonamide hypersensitivity are fever and a maculopapular rash 7 to 14 days after initiating therapy, though a variety of more severe manifestations may occur. The sulfonamide chemical moiety is present in many medications that are not antimicrobials, and fortunately hypersensitivity reactions to these medications are less common. The immunogenicity of sulfonamide antimicrobials may be due to the presence of an arylamine group at the N4 position of the sulfonamide molecule. No diagnostic tests are available to confirm sulfonamide hypersensitivity, and while avoidance of the drug is generally appropriate when a previous hypersensitivity reaction is suspected, desensitization protocols are available for use in HIV patients in whom Pneumocystis carinii pneumonia prophylaxis or treatment is indicated.

Exhaled nitric oxide levels correlate with measures of disease control in asthma.

BACKGROUND: Asthma guidelines emphasize maintaining disease control. However, objective measures of asthma disease control are lacking. OBJECTIVE: We sought to examine the relationship between exhaled nitric oxide (NO) levels and measures of asthma disease control versus asthma disease severity. METHODS: We performed a cross-sectional study of 100 patients (age range, 7-80 years) with asthma. We administered a questionnaire to identify characteristics of asthma, performed spirometric testing before and after administration of a bronchodilator, and measured exhaled NO levels in all participants. RESULTS: Exhaled NO was significantly correlated with the following markers of asthma disease control: asthma symptoms within the past 2 weeks (P =.02), dyspnea score (P =. 02), daily use of rescue medications (P =.01), and reversibility of airflow obstruction (P =.02). Exhaled NO levels were not correlated with the following markers of asthma disease severity: history of respiratory failure (P =.20), health care use (P =.08), fixed airflow obstruction (P =.91), or a validated asthma severity score (P =.19). Markers with relevance to both disease control and severity showed either a weak correlation (FEV(1) and FEV(1) percent predicted) or no correlation (controller drug use) with exhaled NO. CONCLUSION: We conclude that exhaled NO levels are correlated predominantly with markers of asthma control rather than asthma severity. Monitoring of exhaled NO may be useful in outpatient asthma management.

Seasonal variation in bronchial hyperreactivity (BHR) in allergic patients.

As summarized in Table 1, the literature consistently supports the hypothesis that allergic asthmatic patients have seasonal BHR changes that parallel allergen exposure. These seasonal changes appear to be preventable by treatment with corticosteroids (systemic, inhaled, or nasal), disodium cromoglycate, and immunotherapy. Studies have almost exclusively focused on pollens, though similar limited data exist for dust mites. Though the dust mite is a perennial allergen, mite levels are well known to fluctuate with seasonal temperature and humidity trends (44-46), and therefore, seasonal BHR variation in mite-sensitive asthmatic patients is not surprising. Allergenic mold species have not been studied in this regard. In allergic rhinitis patients, the data are less consistent (see Table 2). However, the studies that failed to identify a seasonal BHR difference were either small or had other design limitations. The seasonal changes identified by the larger analyses were similar to those identified for asthmatic patients. Thus, although confirmatory studies would be helpful, it seems likely that in the absence of clinical asthma, allergic rhinitis patients with baseline BHR have allergen-related seasonal changes in BHR. The BHR effects of seasonal changes in air pollution and viral URIs are not known, since they have not yet been directly studied. However, interesting recent reports have identified possible synergistic effects of air pollution exposure on BHR and allergic responses. Similarly, the availability of new viral identification techniques has resulted in the discovery that viral infection may be more prevalent during clinical asthma exacerbation than previously realized. Therefore, air pollution and viral infections may well influence BHR seasonally, and (along with allergens) may contribute to seasonal asthma morbidity and mortality peaks. The mechanism(s) underlying seasonal BHR changes is (are) not known. One plausible possibility with regard to allergen-driven BHR changes involves a type I hypersensitivity late-phase reaction. Characterized by recruitment of eosinophils, lymphocytes, and other cells that are central components of allergic inflammation and are not normally found in the lower airways, this reversible inflammatory process could in turn act, presumably via chemical mediators, on the airway smooth muscle. This may cause bronchoconstriction, but may also increase responsiveness to bronchoconstrictive stimuli independent of bronchoconstriction. This explanation for seasonal BHR changes is supported by findings of blood eosinophil (31,47) and BAL eosinophilic cationic protein (31) level changes that parallel BHR. Prevention of seasonal BHR changes using anti-inflammatory medications (32,33,35) also supports this hypothesis (30) however, and the complex potential interactions between infectious agents and air pollutants on seasonal BHR changes have yet to be studied directly. Therefore, although BHR indeed may predictably vary season to season in allergic individuals, additional investigation is needed to better characterize the reasons for this phenomenon. Further insight in this area may help address the reasons why there are often seasonal epidemics in asthma morbidity and mortality.

Expression of two mRNAs for immunoglobulin lambda chains in the rat.

We have analyzed the expression of immunoglobulin lambda chains in the rat by hybridizing RNA from various sources with C lambda 1-like and C lambda 2-like sequences recovered from a rat genomic library. A 1.0 kb lambda 2-like sequence is readily detected in lambda-producing hybridomas and in normal rat spleen RNAs; a 1.0 kb lambda 1-like message is also present, although at much lower levels. An additional 700 b.p. C lambda 2-like fragment is found in all normal rat spleens, and presumably represents a defective message. The nucleotide sequence of one cDNA clone isolated from the lambda-producing hybridoma G36/1 shows a lambda 2-like sequence, and six lambda-secreting hybridomas produced from the spleen of a kappa-suppressed rat all express a C lambda 2-like message. The great majority of rat lambda chains therefore appear to be lambda 2-like. Northern blot analysis of RNA from the spleen of this kappa-suppressed rat shows a considerable increase in the expression of both lambda 2-like and (at lower levels) lambda 1-like message. The coordinate rise of lambda 1 and lambda 2 RNA in this rat suggests that there may be at least two functional lambda chain genes in the rat, although there is as yet no evidence for the existence of rat lambda 1-like proteins.