We examined the relations between bronchial reactivity, baseline FEV,, and annual decline of height corrected FEV, (A FEV,/ht3) over 7-5 years in 227 men (117 smokers, 71 ex-smokers, and 39 non-smokers). Men with a clinical diagnosis of asthma or receiving bronchodilator treatment were excluded. Bronchial reactivity was determined as the provocation concentration (PC20) of inhaled histamine sufficient to reduce FEV, by 20%; subjects were divided into reactors (PC2, -16 mg/ml) and non-reactors (PC2, >16 mg/ml). Thirty per cent of smokers, 24% of ex-smokers, and 5% of non-smokers were reactors. When smokers who were reactors were compared with non-reactors, the reactors showed a lower baseline FEV, as percentage predicted in 1981-2 (85% v 108%), and a faster AFEV,/ht3 (14.1 v 9-2 ml/y/m3). Baseline FEV, correlated with PC20 in both smokers (rs = 0-51) and ex-smokers (r, = 0.61), and all 15 subjects with an FEV, under 80% of the predicted value were reactors. In ex-smokers AFEV,/ht3 was similar in reactors and non-reactors (m 9-0 v 7-4 mL/y/m3), despite significant differences in baseline FEV,. When analysis was confined to men with a baseline FEV, over 80% predicted, the prevalence of reactors was significantly increased among smokers and slightly increased among ex-smokers compared with non-smokers, though the mean FEV, was higher in the non-smokers. Bronchial reactivity was not increased in smokers aged 35 years or less. In smokers AFEV,/ht3 was faster in those with a personal history of allergy (usually allergic rhinitis), but was not related to a family history of allergic disease, total serum immunoglobulin E level, absolute blood eosinophil count, or skinprick test score. AFEV,/ht3 was also faster in all subjects taking beta blocker drugs. Thus increased bronchial reactivity was associated with accelerated decline of FEV, in smokers. Although the association could be a consequence of a lower baseline FEV,, a trend towards increased reactivity was found in smokers with normal baseline FEV, and AFEV,/ ht3 was dissociated from increased reactivity in ex-smokers. These findings are compatible with the " Dutch hypothesis," but the association between allergic features and accelerated AFEV,/ht3 was relatively weak, and increased reactivity may follow rather than precede the onset of smoking.An overall relationship between cigarette smoking and the development of chronic airflow obstruction has been established.' Nevertheless, there is a very wide range of susceptibility to progressive airflow obstruction among smokers, the cause of which is unknown. More than 20 years ago Dutch research workers2 proposed that smokers with chronic and largely irreversible airflow obstruction shared with

In our experience despite management in a tertiary multidisciplinary bronchiectasis clinic, progression of lung disease continues in a group of children and young adults.

Dutch workers have proposed that people with asthma and those smokers who develop chronic airflow obstruction share a common allergic constitution. To study whether smoking itself is associated with indicators of allergy, we have examined 237 men aged [51][52][53][54][55][56][57][58][59][60][61] years (120 smokers, 73 ex-smokers, and 44 non-smokers) who were recruited to a long term study of lung function in 1974, at which time men with a clinical diagnosis of asthma were excluded. Smokers, ex-smokers, and non-smokers did not differ in personal or family history of allergic disease, but the prevalence of positive responses to skinprick tests was greater in exsmokers (59%) than in the other two groups (33% and 34%). In men with negative responses to skinprick tests total serum IgE was greater in smokers (log,0 mean 1-41 IU/ml) and in ex-smokers (log10 mean 1-53 IU/ml) than in non-smokers (log10 mean 1 12 IU/ml). In men with positive skin test responses serum IgE was similar in the three groups (log10 mean ranging from 1-68 to 1-78 IU/ml). Geometric mean total white cell counts in the peripheral blood were higher in smokers (7.34 x 109/l) than in non-smokers (5.82 x 109/l); the value in ex-smokers (6-16 x 109/l) was intermediate. Absolute blood eosinophil counts were increased in smokers disproportionately to the increase in total white cell count. Thus smoking is associated with small increases in some markers of allergy. These changes are probably acquired after the onset of smoking but sequential studies are required to amplify these cross sectional observations. Smokers whose skin test responses are positive appear more likely to give up smoking.In 1960 Dutch workers' proposed that individuals with asthma and smokers with chronic and mainly irreversible airflow obstruction shared a common allergic constitution and increased non-specific bronchial reactivity. It was not clear whether the increased reactivity followed or preceded the development of airway narrowing.2 In an earlier study from this department Fletcher and coworkers3 found little evidence that allergy contributed to the development of chronic airflow obstruction in smokers; more recently we re-examined some of the younger men in this original study, and in contrast found that the rate of decline of lung function was more rapid in smokers who had some evidence of an allergic constitution than in those who did not.4 Furthermore, a series of reports from Tucson5-7 has investigated the interrelations between atopy, Address for reprint requests: Dr NB Pride, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS. Accepted 8 October 1984eosinophilia, and airflow obstruction and found that blood eosinophilia was associated with impairment of ventilatory function regardless of smoking habit. Smokers have also been shown to have a higher total serum immunoglobulin E (IgE) level than nonsmokers-'4 and a raised white cell count in the peripheral blood. '5-23 These findings have renewed interest in the Dutc...

The baseline value of neutrophil to lymphocyte ratio (NLR) has been found to be prognostic in patients with metastatic castration resistant prostate cancer (CRPC). We evaluated the impact of baseline NLR and its change in patients receiving enzalutamide. We included consecutive metastatic CRPC patients treated with enzalutamide after docetaxel and studies the change of NLR (>3 vs ≤3) after week 4 and 12 weeks. Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Intervals (95% CI) were estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of NLR on PFS and OS was evaluated by Cox regression analyses and on prostate-specific antigen response rates (PSA RR; PSA decline >50%) were evaluated by binary logistic regression. Data collected on 193 patients from 9 centers were evaluated. Median age was 73.1 years (range, 42.8–90.7). The median baseline NLR was 3.2. The median PFS was 3.2 months (95% CI = 2.7–4.2) in patients with baseline NLR >3 and 7.4 months (95% CI = 5.5–9.7) in those with NLR ≤3, p < 0.0001. The median OS was 10.4 months (95% CI = 6.5–14.9) in patients with baseline NLR >3 and 16.9 months (95% CI = 11.2–20.9) in those with baseline NLR ≤3, p < 0.0001. In multivariate analysis, changes in NLR at 4 weeks were significant predictors of both PFS [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 1.07–1.42, p = 0.003, and OS (HR 1.29, 95% CI 1.10–1.51, p = 0.001. A persistent NLR >3 during treatment with enzalutamide seems to have both prognostic and predictive value in CRPC patients.