Effect of high dose vitamin D3 therapy on serum vitamin D3 levels in vitamin D insufficient adults with cystic fibrosis.

BACKGROUND: The effect of a high dose oral cholecalciferol repletion strategy in Vitamin D insufficient adults with CF is still unknown. Therefore, we assessed the effectiveness of our current approach, giving oral vitamin D3 supplementation at a dose of 10,000 IU from Monday to Friday for a total of 50,000 IU D3 weekly in vitamin D insufficient adult with CF. METHODS: We performed a retrospective chart review of all 59 adult CF patients between the ages of 17 and 64 years routinely followed at the CF Adult Program of Winnipeg Health Sciences Centre. Through consultation with the endocrinologist, our clinic vitamin D repletion protocol for treating CF adult patients who have serum 25-hydroxyvitamin D (25-OHD) < 30 ng/ml (<75 nmol/L) was to prescribe vitamin D3 10,000 IU orally from Monday to Friday (or the weekly equivalent of 50,000 IU) for 12 weeks in addition to their regular CF vitamin that supplied from 800 to 2000 IU vitamin D3 daily. Cholecalciferol was conveniently administered orally as either one capsule (oil-based) 10,000 IU or one tablet (powder-based) 10,000 IU. All patients were instructed to obtain follow-up serum 25-OHD levels post completion of treatment. RESULTS: Of the 59 adult patients at our CF Clinic, 35 patients (59%) had below optimal serum 25-OHD levels. Of the 35 patients identified, 10 patients with insufficient serum 25-OHD levels between 10 and 30 ng/ml (25-75 nmol/L) fulfilled the inclusion criteria. A significant increase in serum 25-OHD levels was observed (P < 0.01) from mean value of 21.6 ± 5.9 ng/ml (54.1 ± 14.8 nmol/L) at baseline to 31.7 ± 9.1 ng/ml (79.3 ± 22.8 nmol/L) ≥ 2 months post intervention. The current treatment approach was successful in treating Vitamin D insufficiency in 70% of the patients with low 25-OHD levels. CONCLUSION: The results of this study demonstrate that a large number of adults attending Winnipeg Health Sciences Centre CF Clinic have serum 25-OHD levels below 30 ng/ml (75 nmol/L). This supports the need for dedicated and individualized approach to manage this condition. High dose therapy of vitamin D3, although a more aggressive treatment approach, may result in achieving optimal levels of serum 25-OHD in adults with CF.

Directing therapy in pulmonary arterial hypertension using a target 6 min walk distance.

BACKGROUND: The most effective approaches to escalating advanced therapies in pulmonary arterial hypertension (PAH) are controversial. OBJECTIVE: To compare outcomes before and after introducing a target 6 min walk distance (6MWD) treatment strategy in PAH using registry data. METHODS: From 2001 to 2005, WHO class II to IV patients were treated with bosentan or prostanoids. In July 2005, a target 6MWD strategy was adopted. Monotherapy continued if 6MWD remained >350 m. For patients in whom 6MWD was ≤350 m, sildenafil was added. If 6MWD remained <350 m, prostanoids were considered. Changes in 6MWD, WHO class and survival rate were compared between periods. RESULTS: Before using the 6MWD strategy, there was a statistically significant improvement in mean WHO class at six, nine and 12 months (2.5±0.8 [P<0.015]; 2.5±0.8 [P<0.005]; and 2.5±0.9 [P<0.03], respectively) compared with baseline (2.9±0.9). There was a statistically significant increase in mean 6MWD at three, six, nine and 12 months (383±113 m [P<0.005]; 401±102 m [P<0.006]; 400±109 m [P<0.001]; and 399±110 m [P<0.004], respectively) compared with baseline (321±119 m). The survival rate was 95% at one and two years. From 2005 to 2009, there was a statistically significant improvement in mean WHO class at three, six, nine and 12 months (2.6±0.8 [P<0.05]; 2.3±0.9 [P<0.0001]; 2.3±0.9 [P<0.0001]; and 2.3±1.0 [P<0.0005], respectively) compared with baseline (2.8±0.7). There was statistically significant improvement in 6MWD at six months (381±126 m [P<0.05]), followed by a decline toward baseline (354±117 m). One- and two-year survival rates in the 6MWD target era were 95% and 80%, respectively. CONCLUSION: Based on registry data, adoption of this strategy did not affect survival rates, nor cause a sustained improvement in 6MWD by 12 months. WHO class improved similarly in both treatment groups.

Airway complications post lung transplantation.

PURPOSE OF REVIEW: Advancements in surgical techniques, immunosuppression, graft retrieval, and postoperative care of lung transplant recipients has led to a decline in the incidence of airway complications since the first lung transplant was performed in 1963. Although improved, these complications remain a source of morbidity and mortality for lung transplant recipients. RECENT FINDINGS: Identification and management of risk factors is ideal, although interventional bronchoscopy techniques have allowed management of many airway complications in a less invasive fashion. With current management, mortality related to airway complications is now the same as mortality in lung transplant recipients without airway complications. SUMMARY: This review summarizes the six major classes of airway complications post lung transplantation, with descriptions of radiographic findings and current management.

Addition of sildenafil in patients with pulmonary arterial hypertension with inadequate response to bosentan monotherapy.

BACKGROUND: Pulmonary arterial hypertension (PAH) remains a progressive disease despite improvement when using one of three medication classes: prostanoids, endothelin receptor antagonists or phosphodiesterase-5 inhibitors. Combination therapy has been proposed for patients with unsatisfactory response to monotherapy. OBJECTIVES: To examine the effect of adding sildenafil to bosentan on 6 min walk distance (6MWD) and New York Heart Association (NYHA) classification in patients with PAH who achieved inadequate improvement with bosentan monotherapy. METHODS: Patients with idiopathic PAH or connective tissue disease-associated PAH, and who had either self-reported inadequate improvement in exercise tolerance or a decline in 6MWD after initial improvement, were included in the study (n=10). Data on 6MWD and NYHA class at baseline (before initiation of bosentan), three and six months after baseline, second baseline (before initiation of combination therapy with sildenafil), and three and six months after second baseline were analyzed for any changes. RESULTS: Mean time from initiation of bosentan monotherapy to initiation of combination therapy was 558 days (range 150 to 900 days). Six months after initiation of bosentan, 6MWD increased by 57.2 m above the baseline of 314.4 m. Six months after combination therapy, 6MWD was 62.80 m higher than the baseline before initiation of combination therapy of 339 m (P<0.02). The overall increase in 6MWD six months after combination therapy was higher than the first baseline by 87.4 m (P not significant). NYHA functional class did not improve with combination therapy in all patients. DISCUSSION: Initiating combination therapy in patients who achieve an inadequate improvement in exercise tolerance with monotherapy may result in further improvement in exercise tolerance.

Effect of maintenance azithromycin on established bronchiolitis obliterans syndrome in lung transplant patients.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS), the main cause of late mortality following lung transplantation, is defined as an irreversible decline in forced expiratory volume in 1 s (FEV1). Previous studies using azithromycin for BOS in lung transplant patients have demonstrated a potential reversibility of the decline in FEV1. OBJECTIVES: To examine whether initiating azithromycin reverses decline in FEV1 in lung transplant recipients with established BOS of at least three months. METHODS: Pulmonary function tests were performed every three months in seven lung transplant recipients with established BOS of at least three months. FEV1 was recorded at six and three months before initiation, at time of initiation, and three, six, nine and 12 months postazithromycin initiation. The primary end point was change in FEV1. During the study, no immunosuppressive medication changes or acute rejection episodes occurred. RESULTS: Mean time from transplant to azithromycin initiation was 64 months (range 17 to 117 months). Mean time from BOS diagnosis to azithromycin initiation was 22 months (range three to 67 months). Rate of FEV1 decline from six months before azithromycin initiation, and rates of FEV1 increase from initiation to three and 12 months post-treatment initiation, were not statistically significant (P=0.32, P=0.16 and P=0.18, respectively). Following a trend toward improvement in the first three months after treatment initiation, FEV1 tended to stabilize. DISCUSSION: Although several studies address the possible benefit of maintenance azithromycin in lung transplant patients with BOS, the role of the drug remains unproven in these patients, and would best be addressed by a large randomized controlled trial.