Rationale: One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control. Objectives: To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke. Methods: In a multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast. Measurements and Main Results: Primary outcome was change in prebronchodilator FEV1 in smokers versus nonsmokers. Secondary outcomes included peak flow, PC20 methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV1, bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV1 (170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased a.m. peak flow in smokers (12.6 L/min, p = 0.002), but not in nonsmokers. Conclusions: In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke.

Although guidelines recommend daily therapy for patients with mild persistent asthma, prescription patterns suggest that most such patients use these so-called controller therapies intermittently. In patients with mild persistent asthma, we evaluated the efficacy of intermittent short-course corticosteroid treatment guided by a symptom-based action plan alone or in addition to daily treatment with either inhaled budesonide or oral zafirlukast over a one-year period. In a double-blind trial, 225 adults underwent randomization. The primary outcome was morning peak expiratory flow (PEF). Other outcomes included the forced expiratory volume in one second (FEV₁) before and after bronchodilator treatment, the frequency of exacerbations, the degree of asthma control, the number of symptom-free days, and the quality of life. The three treatments produced similar increases in morning PEF (7.1 to 8.3 percent; approximately 32 liters per minute; P=0.90) and similar rates of asthma exacerbations (P=0.24), even though the intermittent-treatment group took budesonide, on average, for only 0.5 week of the year. As compared with intermittent therapy or daily zafirlukast therapy, daily budesonide therapy produced greater improvements in pre-bronchodilator FEV₁ (P=0.005), bronchial reactivity (P<0.001), the percentage of eosinophils in sputum (P=0.007), exhaled nitric oxide levels (P=0.006), scores for asthma control (P<0.001), and the number of symptom-free days (P=0.03), but not in post-bronchodilator FEV₁ (P=0.29) or in the quality of life (P=0.18). Daily zafirlukast therapy did not differ significantly from intermittent treatment in any outcome measured. It may be possible to treat mild persistent asthma with short, intermittent courses of inhaled or oral corticosteroids taken when symptoms worsen. Further studies are required to determine whether this novel approach to treatment should be recommended.

The authors investigated insulin secretory capacity and insulin action in 11 preoperative patients with pancreatic carcinoma and 15 age‐matched and weight‐matched healthy subjects (C). Five patients were classified as diabetic (D), two as impaired glucose tolerant (IGT), and four as nondiabetic (ND). Postabsorptive serum insulin levels (mean ± SE, in uU/ml) in D (12 ± 2), IGT (17 ± 7), and ND (10 ± 2) were comparable. After administration of 100 g of oral glucose, peak insulin achieved in D (60 ± 11) was lower than in IGT (101 ± 26) and ND (83 ± 20), whereas peak insulin levels in IGT and ND were significantly (P < 0.05) higher than in C (45 ± 6). Comparable insulin response to nonglucose stimuli was documented in all subjects using the slow arginine infusion test with mean serum insulin of 27 ± 4 in D, 28 ± 6 in IGT, 34 ± 10 in ND, and 32 ± 5 in C. In six patients (P) and six controls, insulin action was assessed by the euglycemic hyperinsulinemic clamp technique, with glucose turnover rates estimated by [3‐³H]glucose infusion. Steady‐state plasma glucose concentrations were maintained at 92 ± 3 (P) and 91 ± 1 mg/dl (C). After insulin infusion at the rate of 1.0 mU/kg/min, comparable high physiologic insulin levels were observed in P (73 to 104 uU/ml) and in C (81 to 103 uU/ml). Postabsorptive rates of endogenous glucose appearance (Ra) were higher in P (2.86 to 3.02 mg/kg/min) than in C (1.50 to 2.80 mg/kg/min). At high physiologic insulin concentrations, negative Ra values were documented in all subjects, and complete suppression of Ra was assumed. Total body glucose use (M) was consistently lower in P (3.90 to 6.40 mg/kg/min) than in C (6.98 to 10.40 mg/kg/min), consistent with a state of insulin resistance. Patients with pancreatic cancer manifest insulin resistance by virtue of a decrease in total body glucose use (M) and decreased insulin response to glucose due to either inherent beta cell dysfunction or decreased islet cell mass. The latter is not identifiable by histologic morphology.