Increased Risk of Both Ulcerative Colitis and Crohn's Disease in a Population Suffering from COPD; A. Ekbom, L. Brandt, F. Granath, C.G. Löfdahl, A. Egesten (Lung 2008 May-Jun;186(3):167–72).
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways. In the majority of cases, the inflammation is triggered by tobacco smoke. Smoking also affects the pathogenesis of inflammatory bowel disease (IBD), protecting against ulcerative colitis (UC) and promoting development of Crohn's disease (CD). The present study was undertaken to investigate occurrence of IBD among COPD patients, indicating common inflammatory pathways and shared vulnerability on a genetic basis. The study was designed as a population-based cohort study. All individuals discharged with a diagnosis of COPD from 1987 to 2002 were identified in the Swedish Inpatient Register (n = 180,239). Controls and first-degree relatives of both cases and controls were identified using the Multi-Generation Register. Finally, all individuals (n = 1,174,557) were compared with the Inpatient Register, identifying discharges with a diagnosis of UC or CD. Hazard ratios (HR) for IBD were determined by Cox proportional hazards regression analysis. COPD patients had a significantly higher risk of both UC (HR 1.83; 95% CI 1.61-2.09) and CD (HR 2.72; 95% CI 2.33-3.18). Among first-degree relatives of COPD patients, there was also an overall increased risk of CD (HR 1.25; 95% CI 1.09-1.43) but not of UC (HR 1.09; 95% CI 0.96-1.23). The kinship of first-degree relatives displayed an increased risk of both UC and CD among siblings (HR 1.49; 95% CI 1.15-1.91 and HR 1.46; 95% CI 1.12-1.89, respectively). The results suggest that COPD and IBD may have inflammatory pathways in common, including genetic variants of genes predisposing for disease.
Comments: The authors assembled this cohort from the Swedish Inpatient Register and looked at diagnostic codes on discharge and patients' national registration numbers which gains access information on inpatient care. Patients had to be at least 40 years of age to be included. They then accessed a Multi Generation Register to look for first degree relatives with diagnoses of COPD and IBD. This article not only highlights the fact that there may be certain shared inflammatory pathways for IBD and COPD and hence the possibility that exacerbations of one may cause worsening of the other condition, but also it reminds us that IBD should be in the differential diagnosis as an etiology for chronic obstructive lung disease particularly for those who are non smokers.
Acute Effects of Sildenafil on Exercise Pulmonary Hemodynamics and Capacity in Patients with COPD. S. Holverda, H. Rietema, H. J. Bogaard, N. Westerhof, P. E. Postmus, A. Boonstra, A. Vonk-Noordegraaf (Pulm Pharmacol Ther 2008;21(3):558–64).
Background: We investigated in chronic obstructive pulmonary disease (COPD) patients whether a single dose of sildenafil can attenuate the exercise-induced increase in pulmonary artery pressure, thereby allowing augmentation of stroke volume (SV), and improving maximal exercise capacity. METHODS: Eighteen COPD patients (GOLD II-IV) underwent right heart catheterization at rest and submaximal exercise. Mean pulmonary artery pressure (mPpa) and cardiac output (CO) were assessed. Resting and exercise measurements were repeated 60 min after oral intake of 50 mg sildenafil. Also, on different days, patients performed two maximal exercise tests (CPET) randomly, 1h after placebo and after 50mg sildenafil. RESULTS: Five COPD patients had pulmonary hypertension (PH) at rest (mPpa >25 mmHg) and six developed PH during exercise (mPpa >30 mmHg). In all patients, mPpa increased from rest to submaximal exercise (23+/−10-35+/−14 mmHg). After sildenafil mPpa at rest was 20+/−10 mmHg, in exercise mPpa was increased less to 30+/−14 mmHg (p<0.01). The reduced augmentation in mPpa was not accompanied by an increased SV and CO. In COPD patients with PH the percentage increase in mPpa to submaximal exercise was 68% before, and 51% after oral intake of sildenafil (p = 0.07). In COPD without PH, these values were 46% and 41% (ns), respectively. Maximal exercise capacity and CPET characteristics were unchanged after sildenafil. CONCLUSION: Regardless of mPpa at rest, sildenafil attenuates the increase in mPpa during submaximal exercise in COPD. This attenuated increase is neither accompanied by enhanced SV and CO, nor by improved maximal exercise capacity.
Comments: There remains ongoing debate about the efficacy of PDE-5 inhibitors in treating the pulmonary hypertension associated with COPD. While theoretically there would appear to be potential benefits this paper demonstrates no objective improvements in exercise tolerance for patients with COPD. It would be interesting to know if there are any cumulative effects of using PDE-5 inhibitors as these studies were done after only one dose of drug versus placebo. In addition, it would be interesting to know if subjects found improved tolerance for performing activities of daily living or submaximal exercise activities as they were only tested for maximum exercise capacity on drug versus placebo. Also it would be interesting to see if there is a dose relationship; patients were only studied on one dose in this study and not all patients had baseline pulmonary hypertension. Hence while the findings are interesting, the small number of patients and the limited outcomes studied suggests that more studies are needed to assess potential benefit and perhaps identify patient phenotypes that are more likely to gain benefit from use of these medications.
Sildenafil Treatment in COPD Does not Affect Stroke Volume or Exercise Capacity. H. Rietema, S. Holverda, H. J. Bogaard, J. T. Marcus, H. J. Smit, N. Westerhof, P. E. Postmus, A. Boonstra, A. Vonk-Noordegraaf. (Eur Respir J. 2008 Apr;31(4):759–64).
In chronic obstructive pulmonary disease (COPD) patients, stroke volume response to exercise is impaired. The aim of the present study was to investigate whether 3 months of sildenafil treatment improves stroke volume and, if so, whether this improvement is related to the pulmonary artery pressure and translated into an improved exercise capacity. A total of 15 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) underwent right heart catheterisation at rest and during exercise. Stroke volume was assessed by magnetic resonance imaging (MRI) at rest and during submaximal exercise in the supine position and compared with eight age-matched controls. Additionally, a cardiopulmonary exercise test and a 6-min walking distance test were performed. Exercise tests and MRI were repeated after 12 weeks of oral therapy with 50 mg sildenafil three times daily. Stroke volume in COPD patients was significantly lower than in healthy controls (62+/−12 versus 81+/−22 mL at rest and 70+/−15 versus 101+/−28 mL during exercise). Pulmonary hypertension (PH) was diagnosed in nine patients and was absent in six. Treatment with sildenafil had no effect on stroke volume or exercise capacity. Although the stroke volume was lower in COPD patients with associated PH in comparison with non-PH patients, there was no difference in treatment response between both groups. In the present group of 15 chronic obstructive pulmonary disease patients, a reduced stroke volume was found at rest and during exercise. Neither stroke volume nor exercise capacity were improved by 3 months of sildenafil therapy. PMID: 18094009
Comments: Addressing some of the issues mentioned above the same group of authors published subsequent data on a group of 15 patients who received 50 mg sildenafil three times daily for 12 weeks compared to a group of healthy controls but again not all patients with COPD diagnosis had baseline pulmonary hypertension. This study suggests that there remains no clear maximum exercise benefit after 12 weeks of oral therapy. Issues of proper patient selection and benefits with regard to quality of life and or newer composite scores of activities of daily living and sub maximal exercise capacity need to be further assessed. The long term benefits of reducing or indeed preventing the development of cor pulmonale need further study.