Background-Nitric oxide (NO) may be bronchoprotective in asthma, possibly due to a direct action on airway smooth muscle or through mast cell stabilisation. To investigate this the eVects of two doses of nebulised N G -nitro-L-arginine methyl ester (L-NAME), a non-selective NO synthase (NOS) inhibitor, on exhaled NO levels and airway responsiveness to histamine, a direct smooth muscle spasmogen, and adenosine-5'-monophosphate (AMP), an indirect spasmogen which activates mast cells, were evaluated in patients with mild asthma. Methods-The study consisted of two phases each with a double blind, randomised, crossover design. In phase 1, 15 subjects inhaled either L-NAME 54 mg or 0.9% saline 30 minutes before histamine challenge. Nine of these subjects were studied in a similar fashion but were also challenged with AMP. In phase 2, 13 subjects (eight from phase 1) performed the same protocol but inhaled L-NAME in a dose of 170 mg or 0.9% saline before being challenged with histamine and AMP. Results-The mean (95% CI) reduction in exhaled NO levels after L-NAME 54 mg was 78% (66 to 90) but this did not alter airway responsiveness; the geometric mean (SE) concentration provoking a fall of 20% or more in forced expiratory volume in one second (PC 20 ) after L-NAME and saline was 0.59 (1.26) and 0.81 (1.26) mg/ml, respectively, for histamine and 20.2 (1.7) and 17.2 (1.6) mg/ml, respectively, for AMP. In contrast, L-NAME 170 mg reduced NO levels to a similar extent (81% (95% CI 76 to 87)) but increased airway responsiveness by approximately one doubling dose to both spasmogens; the geometric mean (SE) PC 20 for histamine after L-NAME 170 mg and saline was 0.82 (1.29) and 1.78 (1.19) mg/ml, respectively (p<0.001), and for AMP was 11.8 (1.5) and 24.3 (1.4) mg/ml, respectively (p<0.001). Conclusions-These results suggest that L-NAME increases airway responsiveness in asthma. This may occur through mechanisms separate from NO inhibition or through pathways independent of those responsible for production of NO measured in exhaled air. (Thorax 1998;53:483-489)

1 The aim of the present study was to investigate the role of adenosine A2b receptors in the antiproliferative action of theophylline in human peripheral blood mononuclear cells (HPBMC) from healthy and asthmatic subjects. 2 Theophylline signi®cantly inhibited PHA-induced proliferation of HPBMC from both healthy and asthmatic donors but only at relatively high concentrations at 1 mM (P50.05). Enprophylline, a drug which also acts as a non-selective phosphodiesterase (PDE) inhibitor and is a selective A2b receptor antagonist, had no signi®cant e ect on proliferation of cells from either group at concentrations up to 10 mM (P40.05; n=6). 3 Adenosine deaminase (2 u ml 71 ), which metabolizes adenosine, had no signi®cant e ect on PHA-induced HPBMC proliferation over a range of concentrations (0 ± 8 mg ml 71 ) in cells from either healthy or asthmatic subjects. 4 The adenosine receptor agonists N 6 -cyclopentyladenosine (CPA, A1-selective) and 5'-Nethylcarboxamidoadenosine (NECA, A1/A2) produced a small but signi®cant inhibition of PHAinduced proliferation of HPBMC from healthy and asthmatic subjects (10 mM, P50.05; n=6). In contrast, 5'-N-ethylcarboxamido-2-[4-(2-]carboxyethyl)phenethyl]adenosine (CGS21680, A2a-selective) was without signi®cant e ect (P40.05; n=6). 5 The adenosine receptor antagonist alloxazine (A2b-selective) had no signi®cant e ect, while 8(3-chlorostyryl)ca eine,(CSC, A2a-selective) signi®cantly inhibited PHA-induced proliferation of HPBMC from both groups (P50.05; n=6). 6 Our results suggest that endogenous or exogenous adenosine has little e ect on the proliferation of HPBMC obtained from healthy or asthmatic subjects. Thus it would appear that the e ect of high concentrations of theophylline is not related to adenosine receptor antagonism.

Background: Pulmonary nodules are increasingly detected on screening and routine chest imaging, leading to an increase in diagnostic procedures. Bronchoscopy with transbronchial biopsy (TBBx) is the most common diagnostic modality, with diagnostic yield between 43% and 86%, largely dependent on the use of navigational modalities. In 2015 a new biopsy tool by Medtronic, the GenCut core biopsy system [GenCut transbronchial needle aspiration (TBNA)], was developed with the intention of improving yield in lung nodule biopsies. Our goal was to determine the efficacy of this new device when used in addition to TBBx.Patients and Methods: This is a prospective observational study of 324 consecutive bronchoscopic lung biopsies in which both TBBx and GenCut TBNA were performed on the same lesion. We recorded patient and nodule characteristics, along with the bronchoscopic modalities used. The primary outcome was the diagnostic yield with the addition of the GenCut TBNA, and the key secondary outcome was the complication rate.Results: Of the 324 nodule biopsies analyzed, 164 (50.6%) were diagnostic via TBBx or GenCut TBNA. In all, 97 (59%) were positive in both TBBx and Gen-Cut TBNA, 43 (26.2%) were positive only in TBBx, and 24 (14.6%) were positive only in GenCut TBNA. Overall, the addition of the GenCut TBNA increased the diagnostic yield by 7.4% (P < 0.01). There were 7 complications: 5 pneumothoraxes and 2 episodes of bleeding. Conclusion:The diagnostic yield is improved by using the GenCut core biopsy system in addition to traditional TBBx forceps when performing bronchoscopy for pulmonary nodules, without an increase in complications. These biopsy methods should be used in tandem for the greatest yield.

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