Publications

BACKGROUND

The introduction of leukotriene modifiers, the first novel class of medications for asthma in more than 2 decades, provided an opportunity to evaluate the clinical context in which patients receive new treatments. Because milder asthma is usually controllable with more familiar medications, we hypothesized that adults with asthma would receive leukotriene modifiers for more severe disease.

METHODS

We conducted a prospective, longitudinal, 18-month cohort study of 349 patients with asthma. We evaluated the association of baseline self-reported medication use and measures of asthma severity. We also examined the impact of baseline measurement of asthma severity on incident leukotriene modifier use at follow-up.

RESULTS

At baseline, 39 (11%) of 349 patients reported leukotriene modifier use during the previous 2 weeks (95% confidence interval [CI], 8%-15%). Adults with asthma who reported recent use of leukotriene modifiers were more likely to indicate use of other long-term controller medications for asthma, such as inhaled corticosteroids (80% vs 57%;P =.007). Leukotriene modifier use was also associated with poorer severity-of-asthma scores (mean score difference, 3.6 points; 95% CI, 1.7-5.2 points) and asthma-specific health-related quality of life (mean score difference, 8.1 points; 95% CI, 3.4-12.8 points). Leukotriene modifier users were also more likely to indicate a recent emergency department visit (odds ratio [OR], 2.3; 95% CI, 0.9-5.6) or hospitalization for asthma (OR, 4.1; 95% CI, 1.4-11.4). Greater baseline asthma severity was associated with an increased probability of new-onset leukotriene modifier use during 18-month follow-up. Poorer baseline severity-of-asthma scores and asthma-specific quality-of-life scores were related to a greater likelihood of leukotriene modifier use at follow-up (OR per SD-sized score increment, 2.0; 95% CI, 1.4-2.7; OR, 1.8; 95% CI, 1.3-2.5; respectively). Recent hospitalization for asthma at baseline was also associated with a greater likelihood of leukotriene modifier use at follow-up (OR, 4.9; 95% CI, 1.6-14.8).

CONCLUSIONS

Adults with asthma who receive leukotriene modifiers have more severe asthma.

Chronic rapid atrial pacing (RAP) leads to changes that perpetuate atrial fibrillation (AF). Chronic atrial dilatation due to mitral regurgitation (MR) also increases AF inducibility, but it is not clear whether the underlying mechanism is similar. Therefore, we have investigated atrial electrophysiology in a canine MR model (mitral valve avulsion, 1 mo) using high-resolution optical mapping and compared it with control dogs and with the canine RAP model (6-8 wk of atrial pacing at 600 beats/min, atrioventricular block, and ventricular pacing at 100 beats/min). At followup, optical action potentials were recorded using a 16 x 16 photodiode array from 2 x 2-cm left atrial (LA) and right atrial (RA) areas in perfused preparations, with pacing electrodes around the field of view to study direction dependency of conduction. Action potential duration at 80% repolarization (APD(80)) was not different between control and MR but was reduced in RAP atria. Conduction velocities during normal pacing were not different between groups. However, the MR LA showed increased conduction heterogeneity during pacing at short cycle lengths and during premature extrastimuli, which frequently caused pronounced regional conduction slowing. Conduction in the MR LA during extrastimulation also displayed a marked dependence on propagation direction. These phenomena were not observed in the MR RA and in control and RAP atria. Thus both models form distinctly different AF substrates; in RAP dogs, the decrease in APD(80) may stabilize reentry. In MR dogs, regional LA conduction slowing and increased directional dependency, allowing unidirectional conduction block and preferential paths of conduction, may account for increased AF inducibility.