Can measurement of peak expiratory flow enhance compliance in chronic asthma?

Almost all patients with chronic asthma will derive benefit from self-measurement of PEF. Unquestionably, this is of value for educating patients about their disease and treatment, leading in turn to improved compliance. It will be several years before it becomes clear what proportion of patients are willing to manage their asthma themselves and are sufficiently competent in the interpretation of their measurement of PEF to do so safely. It remains to be seen what effect greater use of PEF measurement by patients will have upon present levels of morbidity and mortality from asthma.

A longitudinal study of baseline FEV1 and bronchial responsiveness in patients with asthma.

The effect of initial airway calibre on the response to bronchial provocation is unclear. Theoretically, geometric relationships within the airways might influence the measurement of responsiveness, particularly since a given change in calibre will produce a disproportionately greater reduction in flow in airways which are already narrowed. We have examined the relationship between serial measurements of prechallenge forced expiratory volume in one second (FEV1) and responsiveness to methacholine (PD20) in 8 children and 12 adults with asthma. Measurements were made every 2-3 wks for 12-18 months and all patients kept a daily record of symptoms and twice daily measurements of peak expiratory flow (PEF). Spearman's rank correlation coefficient (rho) for the relationship PD20 versus pre-challenge FEV1 was derived for each patient and varied widely within the group (range -0.22 to 0.73, mean 0.31); the strength of this correlation was not related to a patient's mean FEV1 % predicted, but was related to the degree to which PD20 and pre-challenge FEV1 themselves reflected concurrent asthma severity (mean morning PEF and mean symptom scores for the three days around each test). This suggests that the observed relationship between pre-challenge FEV1 and PD20 may be due less to the influence of airway geometric factors, which might be expected to be present in all patients, but rather that pre-challenge FEV1 is reflecting the severity of the underlying disease. Larger studies will be needed to test this hypothesis further.

Does non-specific bronchial responsiveness indicate the severity of asthma?

It is difficult to analyse the relationship between bronchial responsiveness and the severity of asthma since each alone is difficult to assess. Asthma is a heterogeneous condition with many patterns of expression, and clinical methods used to assess its severity have their limitations. Problems also arise in interpreting the results of bronchial provocation tests and methodological differences make comparisons between studies difficult. The findings of both cross-sectional and longitudinal studies have shown a general relationship between the degree of responsiveness and the severity of asthma, but within subjects the relationship is weaker. A greater understanding must await increased knowledge of the mechanisms underlying asthma and the contribution which hyperresponsiveness makes to each of these.

Nonspecific bronchial reactivity and its relationship to the clinical expression of asthma. A longitudinal study.

The contribution of nonspecific bronchial reactivity to the day-to-day clinical expression of asthma is uncertain. We have examined this relationship in a longitudinal study of eight children and 12 adults. Measurements of reactivity to methacholine were made every 2 to 3 wk over a period of 12 to 18 months, deriving the dose that caused a 20% fall in FEV1 (PD20). Throughout the study, all patients kept a daily record of symptoms and treatment and twice daily measurements of peak expiratory flow (PEF). A significant relationship was found between subjects' overall reactivity (median PD20) and both their average day-to-day variation in morning PEF (Spearman's rho = -0.53, p = 0.016) and diurnal variation in PEF (Spearman's rho = -0.60, p = 0.004). However, examining the temporal relationship between reactivity and asthma within subjects, individual PD20 measurements were not consistently related to concurrent asthma severity: in only six subjects did changes in PD20 generally reflect simultaneous trends in symptoms or PEF. In several patients, exacerbations of asthma occurred in the absence of bronchial hyperreactivity (PD20 greater than 12.8 mumol). We conclude that nonspecific bronchial reactivity is only one mechanism underlying airflow obstruction in asthma, and that its relationship to the clinical state of asthma is not sufficiently close to be of practical clinical use.

New regression equations for predicting peak expiratory flow in adults.

An earlier study of peak expiratory flow (PEF) in normal adults contained too few men aged over 55 and women aged over 65 for the regression equations to be used for prediction in older people. A subsequent study was therefore carried out on an additional 23 men and 29 women aged 55 or over who were lifelong non-smokers and satisfied the same strict criteria of normality that had been used in the original study. The data from both studies were combined and a new model used to calculate equations for the regression of PEF on age and height in the two sexes. With this model predicted values could be derived for men and women aged between 15 and 85. These new equations gave predicted values in men and women aged less than 55 and 65, respectively, which were almost identical with those reported previously. The new regression equations for PEF enable values to be predicted for people aged 15-85 and so enhance the accuracy of testing in the elderly.

Peak expiratory flow in symptomless elderly smokers and ex-smokers.

Values of peak expiratory flow (PEF) in 142 current smokers (116 men, 26 women) and 108 ex-smokers (88 men, 20 women) aged 55 or over were compared with the predicted values obtained in lifelong nonsmokers of the same age range. None of the subjects had been liable during childhood or subsequently to expectoration, lower respiratory tract infection, wheeze, or shortness of breath. Observed values of PEF were expressed as differences from predicted. Analysis of the relation between smoking state and ventilatory function in the men disclosed significant reductions of PEF in current smokers, the deficits increasing with the amount smoked from a mean of 48.1 l/min in those smoking fewer than 20 cigarettes a day to 73.3 l/min in smokers of 20 or more a day. Significant reductions of PEF were also found in women who were currently smoking (mean 47.4 l/min) and in male ex-smokers of 20 or more cigarettes a day (mean 27.8 l/min). There was no significant reduction of PEF in male or female ex-smokers of fewer than 20 cigarettes a day. These findings suggest that factors besides smoking are concerned in the development of irreversible airflow obstruction.

Generation of lymphokine-activated killer cells in strain 2 guinea pigs and their use in the therapy of L2C, an acute B-cell leukemia.

Lymphokine-activated killer (LAK) cells were induced by incubating strain 2 guinea pig splenocytes or lymph node-derived cells in recombinant human interleukin-2 (IL-2) for 3-5 days. These effector cells had the morphology of lymphoblasts and were able to lyse murine P815 tumor cell targets. Fresh, unstimulated, guinea pig effectors were not capable of lysing these targets. The therapy of the L2C leukemia, an acute B-lymphoblastic leukemia of strain 2 guinea pigs, using LAK cells and recombinant IL-2 was examined. Antitumor effects were demonstrated by premixing LAK and tumor cells prior to intradermal injection in Winn type assays and then measuring the growth of local tumor and survival of the animals. In further experiments i.p. administration of LAK cells, 4 h following tumor cell inoculation by the i.p. route, prolonged the survival of treated animals. The best results in this i.p. therapy model were obtained with a 10-fold excess of LAK cells over tumor cells plus additional treatment with 1000 units of IL-2 for 20 days. This resulted in a 10-day increase in median survival of treated animals. Despite these in vivo antitumor effects, lytic activity of LAK effector populations against L2C targets could not be demonstrated in vitro. The potential synergy between LAK cells, IL-2, and a monoclonal antibody directed against the idiotype of the neoplastic cell surface immunoglobulin was also investigated. In these experiments enhanced survival of the combined treatment group, beyond that of either singly treated group, was not found. This study shows that LAK cells are useful agents in the therapy of a widely disseminated, aggressive, B-cell lymphoblastic leukemia. The use of such effectors, even in cases where in vitro lysis of the target tumor cell cannot be demonstrated, is encouraged by these results.