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Inflammatory reactions are believed to be important in nonspecific bronchial hyperreactivity (BHR). To investigate the potential role for oxidant-mediated modulation of BHR, we investigated oxidative metabolism of polymorphonuclear leukocytes (PMN) from the peripheral blood in 28 nonallergic patients with chronic air-flow obstruction (CAO). No difference in O2- was found between 14 smokers and 14 ex-smokers with CAO. A significant correlation was found between the degree of BHR and O2(-)-generation of PMN after stimulation with 20 ng/ml phorbol myristate acetate, both in smokers (r = 0.59, p less than 0.01) and in ex-smokers (r = 0.79, p less than 0.01). In the light of other findings in experimental animal studies, the results suggest a direct or indirect role for O2- in the modulation of BHR. Thus, in nonallergic patients with CAO, BHR and inflammation may be linked in a similar way as in allergic patients with asthma.

Conclusions-This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV 1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids.

IntroductionIn randomly assigned studies with EGFR TKI only a minor proportion of patients with NSCLC have genetically profiled biopsies. Guidelines provide evidence to perform EGFR and KRAS mutation analysis in non-squamous NSCLC. We explored tumor biopsy quality offered for mutation testing, different mutations distribution, and outcome with EGFR TKI.Patient and MethodsClinical data from 8 regional hospitals were studied for patient and tumor characteristics, treatment and overall survival. Biopsies sent to the central laboratory were evaluated for DNA quality and subsequently analyzed for mutations in exons 18–21 of EGFR and exon 2 of KRAS by bidirectional sequence analysis.ResultsTumors from 442 subsequent patients were analyzed. For 74 patients (17%) tumors were unsuitable for mutation analysis. Thirty-eight patients (10.9%) had EGFR mutations with 79% known activating mutations. One hundred eight patients (30%) had functional KRAS mutations. The mutation spectrum was comparable to the Cosmic database. Following treatment in the first or second line with EGFR TKI median overall survival for patients with EGFR (n = 14), KRAS (n = 14) mutations and wild type EGFR/KRAS (n = 31) was not reached, 20 and 9 months, respectively.ConclusionOne out of every 6 tumor samples was inadequate for mutation analysis. Patients with EGFR activating mutations treated with EGFR-TKI have the longest survival.