Acetazolamide has been investigated for treating sleep apnea in newcomers ascending to high altitude. This study aimed to assess the effect of acetazolamide on sleep apnea at high altitude, determine the optimal therapeutic dose, and compare its effectiveness in healthy trekkers and obstructive sleep apnea (OSA) patients.
PubMed, Embase, Scopus, Cochrane Library, and Airiti Library databases were searched up to July 2015 for randomized controlled trials (RCTs) performed above 2500 m in lowlanders and that used acetazolamide as intervention in sleep studies. Studies including participants with medical conditions other than OSA were excluded.
Eight studies of 190 adults were included. In healthy participants, the pooled mean effect sizes of acetazolamide on Apnea–Hypopnea Index (AHI), percentage of periodic breathing time, and nocturnal oxygenation were 34.66 [95% confidence interval (CI) 25.01–44.30] with low heterogeneity (p = 0.7, I2 = 0%), 38.56% (95% CI 18.92–58.19%) with low heterogeneity (p = 0.24, I2 = 28%), and 4.75% (95% CI 1.35–8.15%) with high heterogeneity (p < 0.01, I2 = 87%), respectively. In OSA patients, the pooled mean effect sizes of acetazolamide on AHI and nocturnal oxygenation were 13.18 (95% CI 9.25–17.1) with low heterogeneity (p = 0.33, I2 = 0%) and 1.85% (95% CI 1.08–2.62%) with low heterogeneity (P = 0.56, I2 = 0%).
Acetazolamide improves sleep apnea at high altitude by decreasing AHI and percentage of periodic breathing time and increasing nocturnal oxygenation. Acetazolamide is more beneficial in healthy participants than in OSA patients, and a 250 mg daily dose may be as effective as higher daily doses for healthy trekkers.
Endoscopic lung volume reduction coil (LVRC) treatment is an option for selected patients with severe emphysema. In the advanced stages, emphysema leads to respiratory failure: hypoxemia and eventually chronic hypercapnic respiratory failure. It can be hypothesized that LVRC treatment, a procedure targeting hyperinflation and thereby reducing ventilatory workload, may be especially beneficial in patients with chronic hypercapnic respiratory failure. This study was conducted to gain first insights into the effects and the safety of LVRC treatment in patients with emphysema and chronic hypercapnic respiratory failure.
A retrospective observational study conducted in the Department of Respiratory Medicine at the University Medical Center Hamburg-Eppendorf, Germany on all patients with chronic hypercapnic respiratory failure in whom bilateral LVRC treatment was performed between 1 April 2012 and 30 September 2015.
During the study period, bilateral LVRC treatment was performed in 10 patients with chronic hypercapnic respiratory failure. Compared with baseline, bilateral LVRC treatment led to a significant increase in mean forced expiratory volume in one second (FEV1) from 0.5 ± 0.1 l to 0.6 ± 0.2 l (p = 0.004), a decrease in residual volume (RV) from 6.1 ± 0.9 l to 5.6 ± 1.1 l (p = 0.02) and a reduction in partial pressure of carbon dioxide in arterial blood (PaCO2) from 53 ± 5 mmHg to 48 ± 4 mmHg (p = 0.03). One case of hemoptysis requiring readmission to hospital was the only severe adverse event.
LVRC treatment was safe and effective in patients with nonsevere chronic hypercapnic respiratory failure. It led not only to an improvement in lung function but also to a significant decrease in PaCO2.
Placement of endobronchial valves for bronchopleural fistula (BPF) is not always straightforward. A simple guide to the steps for an uncomplicated procedure does not encompass pitfalls that need to be understood and overcome to maximize the efficacy of this modality.
The objective of this study was to discuss examples of difficult cases for which the placement of endobronchial valves was not straightforward and required alterations in the usual basic steps. Subsequently, we aimed to provide guiding principles for a successful procedure.
Six illustrative cases were selected to demonstrate issues that can arise during endobronchial valve placement.
In each case, a real or apparent lack of decrease in airflow through a BPF was diagnosed and addressed. We have used the selected problem cases to illustrate principles, with the goal of helping to increase the success rate for endobronchial valve placement in the treatment of BPF.
This series demonstrates issues that complicate effective placement of endobronchial valves for BPF. These issues form the basis for troubleshooting steps that complement the basic procedural steps.
Asthma affects a large number of patients in China, but relatively little is known about asthma management among Chinese patients. This study aims to estimate asthma control rate among adult Chinese patients and to identify predictors associated with uncontrolled asthma.
A total of 4125 asthma patients aged >=17 years and representing all regions of mainland China except Tibet were surveyed. Asthma control status was assessed using the Asthma Control Test (ACT) and classified as controlled (ACT score >= 20) and uncontrolled (ACT score 19). A multivariate logistic regression model was used to identify predictors associated with uncontrolled asthma from the factors including demographics, rhinitis, allergic rhinitis, and treatment adherence.
Asthma was controlled in 44.9%, and uncontrolled in 55.1% of the study participants. High rates of uncontrolled asthma were found in patients with treatment nonadherence (77.3%), poor adherence (66.2%), no schooling (64.8%), or obesity (62.9%). The risk of uncontrolled asthma was much higher in the treatment nonadherence group than the complete adherence group [odds ratio (OR) = 4.55 (3.68–5.62), p < 0.001]. Other predictors for uncontrolled asthma included concomitant rhinitis [OR = 1.31 (1.14–1.50), p < 0.001], obesity [OR = 1.31 (1.05–1.64), p = 0.019], asthma duration > 3 years [OR = 1.22 (1.07–1.39), p = 0.004] and age >= 45 years [OR = 1.23 (1.07–1.41), p = 0.004].
About half of the participants in this study had uncontrolled asthma. Treatment nonadherence is one of the significant predictors, which is very strongly associated with uncontrolled asthma. Efforts should be prioritized to promote patients’ treatment adherence to improve asthma control while attention is needed on rhinitis or obesity.
Bronchial occlusion with an Endobronchial Watanabe Spigot (EWS) has been shown to be useful in managing prolonged bronchopleural fistulas and intractable hemoptysis. EWS bronchial occlusion using a curette is less technically demanding. This retrospective study evaluated the clinical utility and simplicity of this method.
A total of 18 consecutive patients (15 men, 3 women, aged 47–85 years) who underwent bronchial occlusion using an EWS from April 2012 to August 2014 were evaluated. The method involves sticking the tip of a curette into an EWS to the first joint, allowing it to be turned in any direction or at any angle. The time required to occlude the target bronchus was measured on routinely recorded digital videos. Other parameters evaluated included success rates, complications, and clinical outcomes.
Of the 18 patients, 11 underwent bronchial occlusion for intractable pneumothorax, 5 for postoperative bronchopleural fistula, two for intractable empyema, and one for hemoptysis. Each patient required 1–7 EWSs (median 4). Target bronchi included the right upper (n = 8), left upper (n = 5), right lower (n = 2), left lower (n = 2), and right middle (n = 1) bronchi. The success rate of EWS insertion into the target bronchus was 100%. Time per EWS occlusion ranged from 65–528 sec (median 158.5 sec). Of the 62 insertions, 36 (58.1%) were completed within 3 min, and 58 (93.5%) within 5 min. Successful outcomes were observed in 15 (83.3%) of the 18 patients.
EWS bronchial occlusion using a curette is a simple method for managing intractable bronchopleural fistulas in daily clinical settings.
The aim of this study was to determine the influence of selected physiological, psychological and situational factors on experience of fatigue, and functional limitations due to fatigue in patients with stable chronic obstructive pulmonary disease (COPD).
In total 101 patients with COPD and 34 control patients were assessed for experience of fatigue, functional limitation due to fatigue (Fatigue Impact Scale), physiological [lung function, 6-minute walk distance (6MWD), body mass index (BMI), dyspnoea, interleukin (IL)-6, IL-8, high sensitivity C-reactive protein (hs-CRP), surfactant protein D], psychological (anxiety, depression, insomnia), situational variables (age, sex, smoking, living alone, education), and quality of life.
Fatigue was more common in patients with COPD than in control patients (72% versus 56%, p < 0.001). Patients with COPD and fatigue had lower lung function, shorter 6MWD, more dyspnoea, anxiety and depressive symptoms, and worse health status compared with patients without fatigue (all p < 0.01). No differences were found for markers of systemic inflammation. In logistic regression, experience of fatigue was associated with depression [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.28–2.25) and insomnia (OR 1.75, 95% CI 1.19–2.54). In linear regression models, depression, surfactant protein D and dyspnoea explained 35% (R2) of the variation in physical impact of fatigue. Current smoking and depression explained 33% (R2) of the cognitive impact of fatigue. Depression and surfactant protein D explained 48% (R2) of the psychosocial impact of fatigue.
Experiences of fatigue and functional limitation due to fatigue seem to be related mainly to psychological but also to physiological influencing factors, with depressive symptoms, insomnia problems and dyspnoea as the most prominent factors. Systemic inflammation was not associated with perception of fatigue but surfactant protein D was connected to some dimensions of the impact of fatigue
Although bronchiolitis poses a significant health problem in low- and middle-income countries (LMICs), to the best of our knowledge, to date it has not been determined whether evidence-based bronchiolitis clinical practice guidelines (CPGs) complemented by standardized educational strategies reduce the use of unnecessary diagnostic tests and medications and improve clinically important outcomes in LMICs.
In an uncontrolled before and after study, we assessed the impact of the implementation of an evidence-based bronchiolitis CPG on physician behavior and the care of infants with bronchiolitis by comparing pre-guideline (March to August 2014) and post-guideline (March to August 2015) use of diagnostic tests and medications through an electronic medical record review in a children’s hospital in Bogota, Colombia. We also sought to assess the impact of the implementation of the CPG on clinically important outcomes such as lengths of stay, hospital admissions, intensive care admissions, and hospital readmissions.
Data from 662 cases of bronchiolitis (pre-guideline period) were compared with the data from 703 cases (post-guideline period). On comparing the pre- and post-guideline periods, it was seen that there was a significant increase in the proportion of patients with an appropriate diagnosis and treatment of bronchiolitis (36.4% versus 44.5%, p = 0.003), and there were statistically significant decreases in the use of a hemogram (33.2% versus 26.6%, p=0.010), procalcitonin (3.9% versus 1.6%, p=0.018), nebulized beta-2 agonists (45.6% versus 3.4%, p < 0.001), nebulized anticholinergics (3.3% versus 1.4%, p= 0.029), and nebulized epinephrine (16.2% versus 7.8%, p < 0.001). Likewise, a significant increase in the use of nebulized hypertonic saline was seen (79.6% versus 91.7%, p < 0.001). However, implementation of the CPG for bronchiolitis was not associated with significant changes in clinically important outcomes.
The development and implementation of a good quality bronchiolitis CPG is associated with a significant increase in the proportion of cases with an appropriate diagnosis and treatment of the disease in the context of a university-based hospital located in the capital of an LMIC. However, we could not demonstrate an improvement in clinically important outcomes such as any of the bronchiolitis severity parameters.
Spontaneous pneumomediastinum (SPM) is an uncommon disorder. It is rarely reported in paediatric patients and may be accompanied by subcutaneous emphysema. It is usually benign and self-limiting, with only supportive therapy being needed, but severe cases may require invasive measures. Asthma exacerbations have classically been described as a cause of SPM. However, detailed descriptions in asthmatic children are scarce. We aimed at improving the current understanding of the features of SPM and subcutaneous emphysema, and outcomes, by means of a case report and a systematic review.
For the systematic review a literature search was performed in PubMed to identify reported cases of SPM in asthmatic children.
The case a 10-year-old asthmatic girl with SPM is reported. The patient received an inhaled corticosteroid and long-acting beta2 agonist, in addition to sublingual immunotherapy (SLIT) with eventual control of asthma symptoms. Review: A total of 114 published cases were found since 1995, most of them in teenagers; no sex differences were observed. Clinical presentation was associated with an asthma exacerbation in a number of cases. Other presenting features were chest pain, dyspnoea, cough, and particularly acute swelling of the face, neck, and upper chest. Subcutaneous emphysema was present in most patients. Overall, three cases of pneumothorax and two cases of pneumorrhachis were reported. Therapy was mainly based on supportive care, rest, oxygen therapy, analgesics, steroids, and bronchodilators. All patients recovered spontaneously, in spite of a small initial increase in SPM in a few cases.
Early identification of patients at risk of SPM would avoid the high number of under-diagnosed cases. Patients should be treated not only with supportive therapy but also with measures to achieve control of the underlying cause (such as poorly controlled asthma).
Although lobectomy is still the preferred treatment for patients with stage I non-small cell lung cancer (NSCLC), segmentectomy or wedge resection is frequently performed on patients who cannot withstand the physiological rigors of lobectomy. The objective of this study was to compare the overall survival (OS), cancer-specific survival (CSS), and disease-free survival outcomes among patients with stage I NSCLC who have undergone these procedures.
A systematic electronic search in three online databases was conducted from their earliest publication dates to June 2015. The studies were evaluated according to rigorous, predefined inclusion criteria. The hazard ratio (HR) was used as the outcome measure for data combining.
There were nine eligible studies. These studies included 1181 patients who underwent segmentectomy and 2003 patients who underwent wedge resection. Stage I NSCLC patients who underwent segmentectomy had significantly better OS (HR 0.80; 95% confidence interval [CI], 0.68–0.93; p = 0.004) and CSS (HR 0.42; 95% CI, 0.20–0.88; p = 0.02) rates than those who underwent wedge resection. However, there were no significant differences in OS (HR 0.39; 95% CI, 0.15–1.02; p = 0.06) and CSS (HR 1.87; 95% CI, 0.29–12.06; p = 0.51) rates between segmentectomy and wedge resection in patients with stage Ia NSCLC with tumor size <= 2 cm.
For patients with stage I NSCLC, segmentectomy results in higher survival rates than wedge resection, whereas the outcomes of wedge resection are comparable to those of segmentectomy for patients with stage Ia NSCLC with tumor size <= 2 cm. Considering the limitations and heterogeneity of the included studies, this conclusion should be further confirmed by rigorous randomized clinical trials.
The objective of this study was to compare the cost-effectiveness of the fixed-dose combination (FDC) of tiotropium + olodaterol Respimat® FDC with tiotropium alone for patients with chronic obstructive pulmonary disease (COPD) in the Italian health care setting using a newly developed patient-level Markov model that reflects the current understanding of the disease.
While previously published models have largely been based around a cohort approach using a Markov structure and GOLD stage stratification, an individual-level Markov approach was selected for the new model. Using patient-level data from the twin TOnado trials assessing Tiotropium + olodaterol Respimat® FDC versus tiotropium, outcomes were modelled based on the trough forced expiratory volume (tFEV1) of over 1000 patients in each treatment arm, tracked individually at trial visits through the 52-week trial period, and after the trial period it was assumed to decline at a constant rate based on disease stage. Exacerbation risk was estimated based on a random-effects logistic regression analysis of exacerbations in UPLIFT. Mortality by age and disease stage was estimated from an analysis of TIOSPIR trial data. Cost of bronchodilators and other medications, routine management, and costs of treatment for moderate and severe exacerbations for the Italian setting were included. A cost-effectiveness analysis was conducted over a 15-year time horizon from the perspective of the Italian National Health Service.
Aggregating total costs and quality-adjusted life years (QALYs) for each treatment cohort over 15 years and comparing tiotropium + olodaterol Respimat® FDC with tiotropium alone, resulted in mean incremental costs per patient of 1167 and an incremental cost-effectiveness ratio (ICER) of 7518 per additional QALY with tiotropium + olodaterol Respimat® FDC. The lung function outcomes observed for tiotropium + olodaterol Respimat® FDC in TOnado drove the results in terms of slightly higher mean life-years (12.24 versus 12.07) exacerbation-free months (11.36 versus 11.32) per patient and slightly fewer moderate and severe exacerbations per patient-year (0.411 versus 0.415; 0.21 versus 0.24) versus tiotropium. Probabilistic sensitivity analyses showed tiotropium + olodaterol Respimat® FDC to be the more cost-effective treatment in 95.2% and 98.4% of 500 simulations at thresholds of 20,000 and 30,000 per QALY respectively.
Tiotropium + olodaterol Respimat® FDC is a cost-effective bronchodilator in the maintenance treatment of COPD for the Italian health care system.
Use of varenicline for as long as necessary to achieve abstinence has not been studied. The aim of this study was to test whether smokers with mild-to-moderate chronic obstructive pulmonary disease (COPD) are able to quit if they use varenicline for a sufficient length of time.
A total of 30 heavy smokers with COPD took varenicline for sufficiently long enough for smoking cessation. Smokers were allowed to smoke without a fixed quit date. The main endpoints were the time of voluntary abstinence (VA) and the continuous abstinence rate (CAR) at 12 and 18 months.
Of 28 subjects, eight subjects continued to smoke and 20 subjects stopped smoking, demonstrating a CAR up to 18 months (71%). Median time of treatment was 6 (range 3–24) and 2 (range 1–8) months for abstainers and non-abstainers, respectively, and the median time of VA for abstainers was 4 (range 1–21) months.
Use of varenicline for more than the traditional 12 recommended weeks may be a good strategy to increase the cessation rate in heavy smokers with mild COPD.
The objective of this study was to share our experience in the management of congenital tracheal stenosis (CTS) using self-expanding intraluminal stents in infants.
From January 2010 to August 2012, 31 infants with CTS treated using stents by bronchoscope in pediatric intensive care units (PICUs) were recruited for this study.
Among the 31 patients, 17 were male and 14 were female with their ages ranging from 55 days to 22 months. CTS was associated with congenital heart disease (CHD) in 22 patients. There were no immediate stent-related airway complications. A significant and immediate improvement of respiratory obstruction following stent placement in all 31 patients led to successful weaning from the breathing machine and extubation. Granulation tissue formation as a complication was observed in three (9.7%) patients, but all were successfully managed using cryotherapy. During follow up (up to 24 months), stents in 29 infants remained functional. In seven cases, stents were retrieved under bronchoscope (the same day to 10 months), and three cases required stent replacement (each of the three cases had the stent replaced three times). Nine infants died after stenting due to other causes and two infants abandoned treatment.
Airway stenting may provide an important therapeutic option in infants with CTS.
The present study was conducted to assess the efficacy, safety and tolerability of fluticasone propionate/formoterol fumarate combination therapy (FP/FORM; Flutiform®) compared with fluticasone propionate/salmeterol xinafoate (FP/SAL; Seretide® Evohaler®) in children with asthma.
This was an open-label, randomized, controlled, phase III trial and extension. Patients aged 4–12 years with reversible asthma [% predicted forced expiratory volume in 1 second (FEV1) 60–100%; documented reversibility of >=15% in FEV1] were randomized to receive FP/FORM (100/10 µg b.i.d.) or FP/SAL (100/50 µg b.i.d.) for 12 weeks. Eligible patients completing the 12-week core phase entered a 24-week extension phase with FP/FORM (100/10 µg b.i.d.). The primary efficacy endpoint was the change in predose FEV1 from day 0 to day 84. Secondary efficacy endpoints included change in predose to 2-hours postdose FEV1 from day 0 to day 84, peak expiratory flow rate (PEFR), patient-reported outcomes, rescue-medication use and asthma exacerbations.
In total, 211 patients were randomized and 210 completed the core phase; of these patients, 208 entered and 205 completed the extension phase of the study. Predose FEV1 increased from day 0 to day 84 [FP/FORM, 182 ml; 95% confidence interval (CI), 127, 236; FP/SAL, 212 ml, 95% CI, 160, 265] and FP/FORM was noninferior to FP/SAL: least squares (LS) mean treatment difference: –0.031 (95% CI, –0.093, 0.031; p = 0.026). Secondary efficacy analyses indicated similar efficacy with both therapies. There were no notable differences observed in the safety and tolerability profile between treatments. No safety concerns were identified with long-term FP/FORM therapy, and there was no evidence of an effect of FP/FORM on plasma cortisol.
FP/FORM improved lung function and measures of asthma control with comparable efficacy to FP/SAL, and demonstrated a favourable safety and tolerability profile in children aged 4–12 years.
Aspirin use has been shown to be safe for patients undergoing certain diagnostic bronchoscopy procedures such as transbronchial biopsies and endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration. However, there are no studies documenting the safety of aspirin in patients undergoing therapeutic bronchoscopy. The aim of this study is to evaluate whether aspirin increases the risk of bleeding following therapeutic bronchoscopy.
This was a retrospective study to determine if there was a higher risk of bleeding in patients on aspirin undergoing therapeutic bronchoscopy compared with those not on aspirin. Patient characteristics were reported by cohort using the mean, median, and standard deviation for continuous variables, and using frequencies and relative frequencies for categorical variables.
Of the 108 patients who had multimodality therapeutic bronchoscopy, 17 (15.7%) were taking aspirin and 91 (84.3%) were not on aspirin. Patients in the aspirin group were older than those in the no aspirin group (median age: 66 versus 60 years, p = 0.007). The treatment modalities were similar in both groups except that more patients in the no aspirin group were treated with argon plasma coagulation (APC) compared to the aspirin group (60.4% versus 29.4%, p = 0.031). The estimated blood loss (EBL) between the aspirin and no aspirin groups was not significantly different (mean: 6.0 versus 6.7 ml; median: 5.0 versus 5.0, p = 0.36). Overall, there was no difference in complications between both groups.
Aspirin use was not associated with increased risk of bleeding or procedure-related complications after therapeutic bronchoscopy.
Narrow-band imaging (NBI) is a widely available endoscopic imaging technology; however, uptake of the technique could be improved. Teaching new imaging techniques and assessing trainees’ performance can be a challenging exercise during a 1-day workshop. To support NBI training, we developed an online training tool (Medimq) to help experts train novices in NBI bronchoscopy that could assess trainees’ performance and provide feedback before the close of the 1-day course. The present study determines whether trainees’ capacity to identify relevant pathology increases with the proposed interactive testing method.
Two groups of 20 and 18 bronchoscopists have attended an NBI course where they did a pretest and post-test before and after the main lecture, and a follow-up test 4 weeks later to measure retention of knowledge. We measured their ability to mark normal and abnormal ‘biopsy size’ areas on bronchoscopic NBI images for biopsy. These markings were compared with areas marked by experts on the same images.
The first group results were used to pilot the test. After modifications, the results of the improved test for group 2 showed trainees improved by 32% (total class average normalized gain) in detecting normal or abnormal areas. On follow-up testing, Group 2 improved by 23%.
The overall class average normalized gain of 32% shows our test can be used to improve trainees’ competency in analyzing NBI Images. The testing method (and tool) can be used to measure the follow up 4 weeks later. Better follow-up test results would be expected with more frequent practice by trainees after the course.
Peripheral lung nodules (PLNs) are a common and diagnostically challenging finding. Electronavigational bronchoscopy (ENB) is used to increase the diagnostic yield and is considered safe. Multiple factors have been correlated with a better diagnostic yield. We sought to assess the effect of nodule characteristics and prior workup on the diagnostic yield in ENB.
This was a retrospective chart review of 98 ENB procedures in a community referral center. Two investigators reviewed patients’ charts and images independently. Multiple logistic regression analyses was used to determine if factors such as bronchus sign, ground glass opacification (GGO), distance from pleura, prior use of endobronchial ultrasound (EBUS) and positron emission tomography (PET) had an impact on the diagnostic yield.
We evaluated 98 ENBs performed in 92 patients. Most of the lesions were in the upper lobes. The diagnostic yield was 60%. A PET scan was performed prior to ENB in 47% of cases. EBUS was performed in 24% of cases. Bronchus sign was present in 60% of cases and GGO in only 6% of nodules. The odds ratio for diagnostic yield with a bronchus sign was 1.89 [95% confidence interval (CI): 0.83–4.33] and with nodules showing GGO characteristics it was 4.51 (95% CI: 0.51–39.68). Pneumothorax occurred in 6% of cases.
In our cohort, diagnostic yield was 60% with a 6% pneumothorax rate. A suggestive trend for the presence of bronchus sign on computed tomography scan, albeit statistically nonsignificant, as a predictor for improved diagnostic yield needs to be validated in a larger cohort.
Introduction: Ambrisentan is an oral selective endothelin receptor antagonist licensed for use in pulmonary arterial hypertension (PAH). There are few data on clinical use and long-term tolerability in a wider range of patients with pulmonary hypertension (PH).
Methods: All patients treated with ambrisentan over a 4-year period were identified. Baseline characteristics, liver function test (LFT) results and World Health Organization (WHO) functional class were retrieved from hospital databases.
Results: 272 patients received ambrisentan between March 2009 and June 2013 (32% idiopathic PAH, 36% connective tissue disease PAH, 11% congenital heart disease PAH, 6% portopulmonary hypertension, 1% HIV PAH, 4% PH in association with lung disease, 8% chronic thromboembolic PH and 2% PH in association with sarcoidosis). 33.5% of patients received ambrisentan as monotherapy and 12% received ambrisentan as their initial PH therapy. 18% stopped treatment due to side effects and 12% stopped due to lack of efficacy. Oedema was the most common side effect leading to cessation of therapy, which occurred in 7% of patients. 57% of patients who discontinued ambrisentan due to side effects also discontinued other PAH therapies due to side effects previously or subsequently. Ambrisentan was discontinued in two (<1%) patients due to abnormal LFTs. The 3-year survival in congenital heart disease PAH, idiopathic PAH and systemic sclerosis-associated PAH was 80%, 62%, and 38%, respectively (p = 0.003). Survival was superior in patients in whom WHO functional class improved in response to therapy.
Conclusion: Ambrisentan is used as an initial therapy and as monotherapy in a minority of patients in a large UK PH referral centre. Discontinuation due to side effects, and especially oedema, was higher than reported in previous studies while discontinuation due to abnormal LFTs was very uncommon. A majority of patients who discontinued therapy due to side effects also previously or subsequently discontinued other PAH therapies. Improvement in WHO functional class was associated with superior survival.
In recent years in the management of pulmonary arterial hypertension (PAH), endothelin receptor antagonists (ERAs) represent a well-established class of therapeutic agents with clear beneficial effects. Macitentan (Opsumit®), a dual ERA optimized for efficacy and safety, is the newest drug in the class. Macitentan presents a number of key beneficial characteristics, including increased in vivo preclinical efficacy versus existing ERAs, resulting from sustained receptor binding and physicochemical properties that allow enhanced tissue penetration. The clinical pharmacokinetics studies also indicated a low predilection of macitentan for drug–drug interactions. In the SERAPHIN trial, a phase III long-term study of PAH, macitentan significantly reduced morbidity and mortality by 45% versus placebo, providing sustained long-term improvements in exercise capacity. No association was found between changes in exercise capacity and long-term clinical outcomes, but improved cardiopulmonary hemodynamics were recorded in macitentan-treated patients irrespective of baseline background PAH therapy or World Health Organization functional class. Based on these favorable data, the US Food and Drug Administration approved the 10 mg/day dose in late 2013 and the same process has recently been concluded by the European Medicines Agency.
Objective: To demonstrate the efficacy of tonsil brushing in patients with chronic tonsillitis to remove the microbial biofilm on the tonsil surface using an in vitro model.
Design: Specimens from patients undergoing tonsillectomy were evaluated prior to and following surface cleaning methods, including rinsing and brushing, using scanning electron microscopy (SEM).
Patients: The study population consisted of 25 randomly selected patients with chronic tonsillitis.
Interventions: Specimens were collected and divided into four portions. Each portion received distinct surface cleaning methods and was immediately fixed for SEM examination.
Outcome measures: The biofilm layer on the surface of the tonsils was examined using SEM. The density of the biofilm layer and the degree of persistence of the biofilm after rinsing and brushing were measured.
Results: The surface biofilm of the tonsils in the first group, which were neither brushed nor rinsed, revealed a thick layer of biofilm on the mucosal surface. The second group of tonsils, which were only rinsed, also showed a thick layer of biofilm. The third group of tonsils, which were rinsed following gentle brushing using a soft toothbrush, showed a reduction in the thickness of the biofilm layer. The fourth group of tonsils, which were brushed with a hard brush, was almost devoid of a biofilm layer.
Conclusion: Our results demonstrate that rinsing does not effectively remove the biofilm layer on the tonsil surface. The use of a harder brush was identified as a more powerful means of removing biofilm compared with a soft brush.
Asthma is characterized by recurrent and reversible airflow obstruction, which is routinely monitored by history and physical examination, spirometry and home peak flow diaries. As airway inflammation is central to asthma pathogenesis, its monitoring should be part of patient management plans. Fractional exhaled nitric oxide level (FeNO) is the most extensively studied biomarker of airway inflammation, and FeNO references were higher in Chinese (Asians) than Whites. Published evidence was inconclusive as to whether FeNO is a useful management strategy for asthma. Other biomarkers include direct (histamine, methacholine) and indirect (adenosine, hypertonic saline) challenges of bronchial hyperresponsiveness (BHR), induced sputum and exhaled breath condensate (EBC). A management strategy that normalized sputum eosinophils among adult patients resulted in reductions of BHR and asthma exacerbations. However, subsequent adult and pediatric studies failed to replicate these benefits. Asthma phenotypes as defined by inflammatory cell populations in sputum were also not stable over a 12-month period. A recent meta-analysis concluded that induced sputum is not accurate enough to be applied in routine monitoring of childhood asthma. There is poor correlation between biomarkers that reflect different asthma dimensions: spirometry (airway caliber), BHR (airway reactivity) and FeNO or induced sputum (airway inflammation). Lastly, EBC is easily obtained noninvasively by cooling expired air. Many biomarkers ranging from acidity (pH), leukotrienes, aldehydes, cytokines to growth factors have been described. However, significant overlap between groups and technical difficulty in measuring low levels of inflammatory molecules are the major obstacles for EBC research. Metabolomics is an emerging analytical method for EBC biomarkers. In conclusion, both FeNO and induced sputum are useful asthma biomarkers. However, they will only form part of the clinical picture. Longitudinal studies with focused hypotheses and well-designed protocols are needed to establish the roles of these biomarkers in asthma management. The measurement of biomarkers in EBC remains a research tool.
Objectives: Pharmacologically mediated bronchodilation is important in the management of asthma, and is primarily achieved with β2-agonists. Novel compounds should preferably have a longer duration of action and a better systemic side effect profile than established alternatives at comparable peak bronchodilation. This single-dose crossover study was conducted to investigate and compare with formoterol the bronchodilatory and systemic effects, tolerability and safety of AZD3199, a novel ultra-long-acting β2-agonist (uLABA).
Methods: Patients with asthma (n = 37) were randomized to receive AZD3199 (120, 480, 1920 µg), formoterol (9, 36 µg) or placebo inhaled via a Turbuhaler™. Bronchodilation was evaluated by maximum (Emax) and average 22–26 h (E22–26) forced expiratory volume in 1 second (FEV1). Serum potassium was evaluated by minimum (Emin) and 0–4 h average (Eav) determined from serial measurements. AZD3199 and formoterol were compared on the basis of relative dose potency. Adverse events, clinical laboratory tests and physical examinations were markers for safety and tolerability, with plasma AZD3199 as the indicator of drug exposure.
Results: All active treatments dose-dependently increased Emax and AZD3199 (480 and 1920 µg) and formoterol (36 µg) significantly increased E22–26 versus placebo. Relative dose potency between AZD3199 and formoterol was 50-fold on the microgram scale with respect to Emax and 11-fold with respect to E22–26. Small, dose-dependent effects on potassium, heart rate and QTc were seen after administration of AZD3199 compared with placebo. These well-known dose-related class effects of β2-agonists were mild. Notably, serum potassium suppression was less pronounced after AZD3199 compared with formoterol at similar bronchodilation. Overall, AZD3199 was well tolerated.
Conclusions: AZD3199 480 µg and 1920 µg produced 24-hour bronchodilation. At comparable peak bronchodilator effect, AZD3199 was associated with a lower level of systemic side effects than formoterol. AZD3199 was well tolerated, with no safety concerns identified to preclude further investigation.
ClinicalTrials.gov study identifier: NCT00736489
Background: Central airway obstruction (CAO) is a life-threatening situation. Stent insertion re-establishes patency of the central airways. Self-expanding metallic Y stents have been available since 2005, widening the spectrum of interventional bronchoscopic techniques.
Methods: Retrospective analysis of all patients treated for CAO with a self-expanding metallic Y stent at the Thoraxklinik Heidelberg between May 2005 and January 2009.
Results: A total of 43 patients aged 26–81 had a metallic Y stent inserted endoscopically for the treatment of CAO; 39 of these patients (90.7%) had CAO due to malignant disease, four patients (9.3%) due to benign disease. In all 43 patients, the Y stent was deployed without any complications. A longitudinal follow up was possible in 32 of the 43 patients. The stents remained in situ for an average of 107.1 days (range 1–640 days). In 29 patients with malignant CAO the stenosis was successfully overcome with a Y stent; 11 of these patients died within 6 weeks following stent insertion. On follow up the remaining 18 patients showed immediate improvement of dyspnoea. Eight out of the 18 patients (44.4%) tolerated the stent without problems, two (11.1%) required further stenting, six (33.3%) had complications such as increased secretions, cough, dyspnoea or granulation tissue formation. The stent was removed in one patient (5.6%) due to increased secretions, and in another (5.6%) as the stent was no longer required due to successful tumour-specific therapy.
Conclusion: Placement of Y stents in symptomatic CAO allows for quick relief of symptoms. Severe complications are rare. Stent removal is possible after successful treatment of the primary tumour. However, the prognostic indicator for survival is the underlying malignancy.
Non-cystic fibrosis bronchiectasis (NCFBE), a historically under-recognized chronic respiratory condition, is a significant diagnosis currently experiencing a resurgence of interest in its clinical management. Ciprofloxacin is part of the current armamentarium used in the treatment of the recurrent respiratory tract infections seen in NCFBE. Inhaled ciprofloxacin, a novel method of drug delivery for the fluoroquinolone class, is being actively investigated. The inhaled formulation is designed to enhance drug delivery to the site of infection in the lung while minimizing the risk of systemic toxicity. This review summarizes the pharmacology and pharmacokinetics of ciprofloxacin and the rationale for the development of an inhaled formulation for NCFBE. Preclinical and clinical data regarding current development of inhaled ciprofloxacin formulations is also evaluated. Lastly, the anticipated role of inhaled ciprofloxacin in the management of NCFBE is discussed, including future considerations and potential limitations of therapy.