John R. Cohn

Guidelines for bronchoprovocation on the investigation of occupational asthma: Report of the Subcommittee on Bronchoprovocation for Occupational Asthma

Asthma can be induced or exacerbated at work by several means. Four work-related disorders, characterized by airflow obstruction and airway hyperresponsivene ss, have been described. These include: occupational asthma, byssinosis, the reactive airways dysfunction syndrome, and variable airflow obstruction caused by irritant substances. This committee has elected to focus only on the topic of occupational asthma, which is defined as asthma that is either induced or exacerbated by exposure to a specific (as opposed to an irritant) agent found at work. The Committee has decided to exclude discussion of other causes of asthmatic exacerbations at work, which does not mean that these conditions are not important. It may also, as discussed in other sections of this report, be quite difficult to distinguish an irritant effect from a specific bronchospastic response. A preexisting history of asthma before exposure to the offending agent does not preclude the diagnosis of occupational asthma.

Duration of allergen immunotherapy in respiratory allergy: when is enough, enough?

OBJECTIVES To investigate the duration of effective inhalant subcutaneous immunotherapy (SCIT) reported in the published literature and to determine if any specific biomarkers or clinical predictors exist that may identify patients who will remain in long-term remission after discontinuing treatment. DATA SOURCES Articles were selected from a search of the PubMed database from 1976 to 2006 using the search terms immunotherapy and allergen immunotherapy in combination with venom, allergic rhinitis, asthma, mechanism, efficacy, and duration, as well as articles known to the authors and referenced in review articles. STUDY SELECTION Articles were selected if evaluation of efficacy of the primary allergic disease treated after discontinuation of SCIT was stated as one of the objectives of the study. RESULTS The rate of relapse after discontinuing SCIT ranges from 0% to 55% of patients in the studies reviewed in this article. The length of the specific allergen immunotherapy and allergen type (ie, perennial vs seasonal) may be variables that affect the duration of clinical remission after cessation of SCIT. One study found the duration of SCIT efficacy after discontinuation depended on duration of treatment and correlated with decrease in skin test reactivity. CONCLUSION Until specific tests or clinical markers are identified that will clearly distinguish between patients who will relapse from those who will remain in long-term clinical remission after discontinuing effective allergen immunotherapy, the decision to continue or stop immunotherapy must be individualized.

Respiratory function in singers: Medical assessment, diagnoses, and treatments

Summary A healthy voice depends upon healthy respiration. An understanding of respiratory function is essential in evaluating disorders that affect the voice. This review addresses the assessment of respiratory complaints by history, physical examination, laboratory testing, and endoscopic procedures. Allergy testing and pulmonary function testing are covered in detail. Special problems that confront the professional voice user, such as the need to optimize respiratory function even in mild disease states, exposure to environmental irritants, and the athletic demands of performance, are related specifically to respiratory function. The discussion of diagnosis and treatment of common ailments such as allergic rhinitis and bronchitis is directed toward treatment of the active singer.

Protective action of timolol in acute myocardial ischemia

Timolol, a beta-adrenoceptor blocking agent with little or no cardiodepressant activity, was studied in acute myocardial ischemia in cats. Timolol, at a dose of 25 mug/kg, blocked 75 to 80% of the cardiac response to isoproterenol. This dose also significantly reduced heart rate in cats subjected to acute myocardial ischemia by ligation of the left coronary artery. Timolol significantly prevented the spread of ischemic damage in the myocardium as assessed by (a) curtailing the increase in plasma creatine phosphokinase (CPK) activity, (b) preventing the loss of CPK from the ischemic portion of the myocardium, and (c) restoring the elevated S-T segment of the electrocardiogram toward normal. Timolol did not significantly retard the increase in fragility of lysosomes in ischemic myocardial tissue. The mechanism of the protective effect to timolol on the ischemic myocardium appears to be via reducing myocardial oxygen demand by decreasing heart rate.

Respiratory and glottal efficiency measures in normal classically trained singers

Respiratory and glottal efficiency measures were collected from a pool of 40 classically trained singers with normal larynges. All singers had > or = 3 years of formal classical voice training and were active professional solo classical singers. Mean flow rates were obtained from all subjects to assess glottal efficiency. Additionally, maximum phonation times and phonation quotients were obtained from a subset of the singers. Pulmonary function test data on forced expiratory volume, forced vital capacity, and forced expiratory flow were obtained for all subjects. Results were compared with published normal values, not specifically derived from trained singers, used commonly in voice laboratories. Differences were found, suggesting the need for separate normative data to be used for evaluation of the vocal athlete.

Response of asthma-related voice dysfunction to allergen immunotherapy: a case report of confirmation by methacholine challenge.

Professional singers and other serious voice users are particularly susceptible to alterations in their vocal apparatus. As the support for vocalization, lung function is an essential element of the production of speech and song. Patients have been described who presented with voice complaints along with minimal or no abnormalities on spirometry, but responded to conventional bronchodilator and other asthma therapy. It was proposed that this represented an exercise-induced asthmalike condition, brought on by the hyperventilation associated with performing. The objective of this study was to establish whether improvement in vocalization while performing correlated with a decrease in non-specific bronchial reactivity. We concluded that resolution of vocal complaints in conjunction with a decrease in methacholine reactivity supports the hypothesis that these patients do have an exercise-induced asthmalike condition brought on by airway drying. As with other patients with asthma, it appears to respond to allergy-directed therapy.

ACE inhibitor-induced angioedema.

Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed for blood pressure control and renal protection. ACEI angioedema is a common problem in patients who are taking ACEI, although, in most cases, the disorder is self-limited, and spontaneous episodes of apparently unprovoked angioedema stop with the discontinuation of the medication. In a subset of patients, hospitalization and even intubation are required for airway protection. The diagnosis is made clinically. There are no laboratory studies that establish the diagnosis. However, such investigations help exclude alternative diagnoses as the cause for the patients presentation. Conventional treatment with regimens used to control allergic angioedema is ineffective in this condition. The mechanism of ACEI-induced angioedema is thought to be related to its effect on the kallikrein-kinin system. Kallikrein is a protease that converts high-molecular-weight kininogens into kinins, primarily bradykinin. Medications recently developed, primarily icatibant and ecallantide, to control hereditary angioedema, a disorder also associated with kallikrein-kinin activation, have been used to treat ACEI angioedema with some success. The efficacy of these agents and their optimal use remains to be established by randomized and placebo controlled trials.

Airway reactivity-induced asthma in singers (Arias)

Summary Professional singers are particularly attuned to changes in air flow that can alter their ability to perform. We describe four singers who complained primarily of performance-related vocalization problems, but who had normal larynges and fundamentally good voice technique. All had normal or near-normal spirometry. Subsequent studies revealed evidence of increased airway reactivity, either by response to bronchodilators or to methacholine. All responded to treatment with bronchodilators with improvement in vocal performance. This represents a form of airway reactivity-induced asthma in singers similar to that found with exercise or hyperventilation.

Management of Clopidogrel Hypersensitivity Without Drug Interruption

Clopidogrel hypersensitivity affects up to 6% of treated patients, often leading to discontinuation of the drug. Conventional desensitization protocols incorporate a washout period off medication that may be problematic after percutaneous coronary intervention because premature discontinuation of dual antiplatelet therapy is a major risk factor for stent thrombosis. The purpose of this study was to evaluate a strategy for treating clopidogrel hypersensitivity without drug interruption using corticosteroids and antihistamines to facilitate development of physiologic tolerance. The study population consisted of 25 consecutive patients who developed clopidogrel hypersensitivity after percutaneous coronary intervention and were managed with suppressive therapy using corticosteroids and antihistamines. Treatment success (resolution of hypersensitivity symptoms without interrupting clopidogrel) was assessed, in addition to duration of clopidogrel therapy and adverse cardiac events during late follow-up (mean 670 ± 630 days). The cohort included 19 men and 6 women with a mean age of 62 ± 9 years. Drug-eluting stents were used in 16 patients (64%). Clopidogrel hypersensitivity occurred 6 ± 2 days after drug initiation. Treatment included corticosteroids (5 patients), antihistamines (5 patients), or corticosteroids and antihistamines (15 patients). Patients treated with corticosteroids received tapering courses for a mean of 10 ± 8 days. Treatment was successful with sustained symptom resolution in 22 of 25 patients (88%). Clopidogrel therapy was continued in successfully desensitized patients for 417 ± 369 days and in patients with drug-eluting stents for 529 ± 376 days. There were no deaths, myocardial infarctions, or stent thrombosis during extended follow-up. In conclusion, clopidogrel hypersensitivity can be successfully treated using short-course corticosteroids and antihistamines without interrupting drug therapy. This technique enables long-term continuation of clopidogrel and confers a low risk of adverse cardiac events.

Successful Desensitization to Enfuvirtide after a Hypersensitivity Reaction in an HIV-1-Infected Man

We report a case of successful, rapid desensitization to enfuvirtide after a hypersensitivity reaction in a man with highly drug-resistant human immunodeficiency virus type 1 infection. The patient was desensitized in a monitored intensive care unit and tolerated the rapid desensitization protocol without any serious adverse effects. This case illustrates the ability to safely desensitize patients with limited treatment options who require enfuvirtide therapy.