Asthma in light of patient documents. A factor analytic study.

INTRODUCTION: The aims of the study were to elucidate the disease spectrum of asthma in clinical practice, the interplay of symptoms, tests and background factors in the diagnosis of asthma and the applicability of exploratory factor analysis in analysing patient documents. MATERIALS AND METHODS: The data in this retrospective cross-sectional study included 195 suspect asthma patients from a systematic sample of 2877 outpatients examined in the Pulmonary Clinic of the Tampere University Hospital from 1983 to 1993 and some statistics on the place of residence and place of birth of the patients. The materials on 73 variables were reduced to 9 factors explaining 40% of the variance in a rotated principal component analysis. CONCLUSIONS: The factorial description of the patient documents revealed four types of asthma: "allergic", "seasonal", "nasal" and "obstructive" asthma. These phenotypes became more dominant in this order with increasing age. Skin prick reactions to pollen diminished, whereas reactions to epithelia and house dust mite increased from allergic to obstructive asthma. Some slight differences in the patient characteristics were also found with respect to place of residence and place of birth. The use of factor analysis in clinical practice and organisation was demonstrated.

Extended exhaled NO measurement differentiates between alveolar and bronchial inflammation.

Lower respiratory tract inflammation can be detected by measuring exhaled nitric oxide (NO) concentration at a single exhalation flow rate, but this does not differentiate between alveolar and bronchial NO production. We assessed alveolar NO concentration and bronchial NO flux with an extended method of measuring exhaled NO at several exhalation flow rates in 40 patients with asthma, 17 patients with alveolitis, and 57 healthy control subjects. Bronchial NO flux was higher in asthma (2.5 +/- 0.3 nl/s, p < 0.001) than in alveolitis (0.7 +/- 0.1 nl/s) and healthy control subjects (0.7 +/- 0.1 nl/s). Alveolar NO concentration was higher in alveolitis (4.1 +/- 0.3 ppb, p < 0.001) than in asthma (1.1 +/- 0.2 ppb) and healthy control subjects (1.1 +/- 0.1 ppb). In asthma, bronchial NO flux correlated with serum level of eosinophil protein X (EPX) (r = 0.60, p < 0.001) and bronchial hyperresponsiveness (r = 0.55, p < 0.001). In alveolitis, alveolar NO concentration correlated inversely with pulmonary diffusing capacity (r = -0.55, p = 0.022) and pulmonary restriction. Glucocorticoid treatment or allergen avoidance normalized bronchial NO flux in asthma and decreased alveolar NO concentration toward normal in alveolitis. In conclusion, extended exhaled NO measurement can be used to separately assess alveolar and bronchial inflammation and to assess disease activity/severity in asthma and alveolitis.

Increased bronchial nitric oxide production in patients with asthma measured with a novel method of different exhalation flow rates.

The concentration of nitric oxide (NO) in exhaled air is increased in patients with asthma, suggesting that measuring fractional exhaled NO concentration (FE(NO)) may be used to monitor asthmatic airway inflammation. However, increased FE(NO) is not specific for asthma, as other inflammatory lung diseases may also increase FE(NO). To augment the specificity of FE(NO) measurement, we tested a novel theoretical modelling of pulmonary NO dynamics that allows the approximation of alveolar NO concentration and bronchial NO flux separately by measuring FE(NO) at several exhalation flow rates. We measured FE(NO) at four exhalation flow rates in 10 steroid-naive asthmatics, 5 patients with extrinsic allergic alveolitis, and in 10 healthy controls. Both the asthmatics and the patients with alveolitis had significantly higher FE(NO) than the healthy controls. The increased NO concentration originated from the bronchial level in the asthmatics and from the alveolar level in the patients with alveolitis. In the second part of the study we assessed the repeatability of FE(NO) test, within-day and day-to-day (during two weeks) variation in FE(NO), and the effects of mouth pressure and cigarette smoking on FE(NO) in healthy volunteers. Repeatability of 10 subsequent measurements was high (coefficient of variation (CV) 4.6% +/- 0.4%), and no diurnal variation was found. The day-to-day variation during a 2-week period gave a CV of 10.6% +/- 1.0%. The magnitude of mouth pressure (5-20 cmH2O in adults, 5-40 cmH2O in children) during measurement had no effect on FE(NO). Smoking a cigarette caused a small and transient but statistically significant increase in FE(NO) at 1 and 5 min after smoking. In conclusion, FE(NO) measurement is highly repeatable with low day-to-day variation among healthy subjects. Our results also suggest that the present novel method of measuring FE(NO) at several exhalation flow rates can be used to approximate alveolar and bronchial contributions to FE(NO) separately and thus increase the clinical value of this test.

Bee venom induces high histamine or high leukotriene C4 release in skin of sensitized beekeepers.

Histamine is the principal mediator released in the skin during immediate bee venom allergy but the significance of cysteinyl leukotrienes in these reactions is not known. We measured skin histamine and cysteinyl leukotriene release induced by bee venom in six sensitized beekeepers with the skin microdialysis technique. The skin was dialyzed for 2 h after skin prick test with bee venom, and the release of histamine and leukotriene C4 (LTC4) into the microdialysis fractions was measured. Leukotriene E4 (LTE) and methylhistamine excretion into the urine was assayed and whole blood histamine release test was performed. The release of histamine in the skin was variable: either high delayed, high immediate and delayed, weak release or no marked release. The histamine releasability in the skin correlated with that in whole blood. The three subjects with low histamine release exhibited high LTC4 release in the skin as well as high LTE4 excretion into the urine. Thus, the histamine and LTC4 releases were inversely associated with each other. These differences may explain the variation in the clinical reaction by bee stings in sensitized beekeepers.

Hard metal alveolitis accompanied by rheumatoid arthritis.

Hard metal lung diseases (HML) are rare, and complex to diagnose. We describe the case of a patient with allergic alveolitis accompanied by rheumatoid arthritis. A sharpener of hard metal by trade, our patient was a 45-year-old, nonsmoking Caucasian female who experienced symptoms of cough and phlegm, and dyspnea on exertion. Preliminary lung findings were inspiratory rales in both basal areas, decreased diffusion capacity and a radiological picture resembling sarcoidosis. A high-resolution computed tomography scan indicated patchy alveolitis as well. An open lung biopsy revealed non-necrotizing granulomas consisting of epitheloid cells and surrounded by lymphocytes, plasma cells and a few eosinophils. These cells also occupied the thickened alveolar interstitium. Macrophages in the alveolar spaces, some of them multinuclear, contained dust particles. Hard metal alveolitis is clinically well known and, in this patient, has been described histologically. After the patient had quit working with hard metal and following corticosteroid therapy, pulmonary symptoms and signs were relieved. During this recovery period, however, she contracted rheumatoid arthritis.