Statistical approaches to the identification of late asthmatic reactions

Abstract

Late asthmatic reactions can be difficult to recognize because of their prolonged time course and the confounding effects of superimposed circadian rhythms of ventilatory function. Conventional methods of analysis are rather arbitrary. They depend for example on a 15 or 20% fall in forced expiratory volume in one second (FEV 1 ) from baseline or from time-matched control measurements. We have, therefore, investigated whether statistical approaches applied to individual subjects can assist in the identification of late asthmatic reactions.In two separate series of aerosol inhalation tests, three symptomatic workers, three asthmatic controls and three nonasthmatic controls were challenged blindly with increasing doses of two chemical agents, and saline. One of the agents, sodium isononanoyl oxybenzene sulphonate (SINOS) was a suspected cause of occupational asthma. Prior to the challenges, FEV 1 was measured hourly on three control days. Cumulative late changes on both control and active challenge days were quantified as the area between a line extrapolated from a 10.00 h baseline and the actual measurements from 12.00-22.00 h (the 2-12 h area decrement). The area decrement measurements on control and active challenge days were compared using Student's t-tests. The sensitivity of this method for detecting late asthmatic reactions among potentially positive tests (SINOS challenge tests in the workers) was examined, as was its specificity. The latter was determined from the false positive rate among the negative tests. A second statistical method based on the pooled standard deviation of serial (hourly) FEV 1 measurements was investigated in the same way. In total, the data from 220 challenge and 30 control days were available for analysis.Late responses associated with falls in FEV 1 of 8-16% were statistically significant when a t-test was used to compare area decrement on each active challenge day with three control days. This approach was, therefore, potentially more sensitive than conventional techniques for identifying late asthmatic reactions. The false positive rate was 4%. The serial FEV 1 method was more sensitive, identifying a further five positive tests, but was less specific, with a false positive rate of 7%.These results suggest that when the day-to-day variability of lung function has been estimated from at least three control days, statistical tests can be applied to potential late asthmatic reactions, allowing them to be identified with greater precision than conventional clinical techniques.

Occupational asthma caused by samba (Triplochiton scleroxylon) wood dust in a professional maker of wooden models of airplanes: A case study

“…In our case 18% fall in FEV 1 was recorded in the 2nd and the 5th h after the SOCT. It is suggested by some evidence that in the case of a delayed reaction, FEV 1 fall ≥ 15% may be considered as positive SICT [31][32][33][34][35]. In the presented case occupational history of asthma symptoms, type of exposure, positive results of SPT to occupational allergens, the high level of bronchial hyperresponsiveness as well as significant decrease in FEV 1 and clinical symptoms with bronchial obstruction induced by the specific challenge test confirmed a positive reaction to the occupational allergen.…”

Challenge inhalation tests in the diagnosis of occupational asthma: the guidelines of European Respiratory Society

“…Однако если БА не пол ностью функционально стабилизирована, следует рассмотреть возможность устранения воздействия перед тестированием. Это также целесообразно при оценке вариабельности ОФВ 1 в течение нескольких дней [50]. Наблюдение пациента.…”

“…Эта пороговая величина вы бирается произвольно, и при более рациональном подходе должны учитываться индивидуальные коле бания ОФВ1 при отсутствии специфического воз действия. Такой способ расчета более чувствителен, чем фиксированные пороговые значения [50], но требуются повторные измерения ОФВ 1 в течение по крайней мере 3 дней для адекватной оценки колеба ний этого показателя [50,[104][105][106]. Для интерпрета ции изменений ПСВ после СИПТ единое мнение отсутствует, но при оценке этого параметра также должна учитываться естественная (при отсутствии воздействий) вариабельность ПСВ у данного паци ента; возможно, что вариабельность ПСВ выше та ковой ОФВ 1. Снижение специфической проводимости дыха тельных путей > 50 % (0,5 кПа / с) либо повыше ние специфического бронхиального сопротивле ния > 100 % (превышающее пороговую величину 2 кПа / с) также обычно расценивается как положи тельная реакция на аллергены и производственные вещества [65,107].…”

Occupational asthma due to a widely used soft solder flux not containing colophony

“…OCCUPATIONAL ASTHMA DUE TO A SOFT SOLDER FLUX as a summary measure for any late change in ventilatory function [4]. This method of analysis is complementary to serial measurements of FEV1, but is more responsive to any variability in daily baseline FEV1 because the area decrement is bounded by the extrapolated mean FEV1 over the 30 minutes before the time of challenge each day.…”

“…For 3 days before the challenge tests, she measured FEV1 hourly at home in order to produce control data. From these, the mean FEV1 at each hour was calculated and plotted, together with the "pooled" lower 95% confidence limit (95% CL) [4]. In addition, the "FEV1 area above the curve" from 2-12 h after challenge (area decrement) was calculated : 95% lower confidence limit.…”