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- Idiopathic Pulmonary Fibrosis: Recent Trials and Current Drug Therapy. [JOURNAL ARTICLE]
- Respiration 2013 Nov 25.:353-363.
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with increasing incidence; the median survival is only 35 months and as yet no therapy has been proven to prolong survival. Recent unexpected randomised controlled trial (RCT) results and the conflicting evaluations of drug efficacy by regulatory agencies when considering the approval of pirfenidone have emphasised that we remain in the first stages of both our understanding of disease-relevant therapeutic targets and in our ability to investigate these putative targets with well-designed RCT. Three phase III trials are, however, anticipated to report results in 2014 and there is cautious optimism that we may be entering an era of mechanism-based anti-fibrotic therapies proven by large RCT to modify disease progression. We must now address how to practically translate these therapies safely and with maximal efficacy from a homogenous RCT population to the 'real-life' heterogeneous population of patients with IPF. The role of a formal multi-disciplinary team meeting in a specialist centre with expertise in IPF is key to this. New methodological and ethical research challenges will arise as we enter an era of potential combination therapy; standardized, robust RCT design will be central to meeting these challenges if we are to enable ongoing progress in our aim of increasing both the length and quality of life of patients with IPF. © 2013 S. Karger AG, Basel.
- Role of Endobronchial and Endoscopic Ultrasound in Pulmonary Medicine. [JOURNAL ARTICLE]
- Respiration 2013 Nov 28.
In the last decade, endobronchial ultrasound (EBUS) has evolved into an important tool for diagnostic bronchoscopy in daily practice. EBUS has established as a standard for the diagnosis of hilar or mediastinal lymphadenopathy, as a guidance technique for peripheral pulmonary lesions and for the evaluation of tumor involvement of the tracheobronchial wall or mediastinum. In the meantime, EBUS has also taken a significant role in mediastinal staging in lung cancer patients. However, EBUS plays not only a role in the diagnosis of malignancies, it is also important for the diagnosis of benign disorders. © 2013 S. Karger AG, Basel.
- Effect of Continuous Positive Airway Pressure Treatment for Obstructive Sleep Apnoea on Visual Processing of Degraded Words. [JOURNAL ARTICLE]
- Respiration 2013 Nov 30.
Background: In a previous uncontrolled study, continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA) improved vision in patients with diabetic macular oedema. Objectives: We investigated whether the above improvement in vision (or visual processing) might have been due to reduced sleepiness, rather than a true improvement in retinal function. Methods: Twelve normal control subjects and 20 patients with OSA were tested for their ability to recognise degraded words, by means of a computer programme displaying 5-letter words every 4 s for 10 min, with variable amounts of the bottom half of the word missing; the percentage of the word necessary to achieve correct identification on average half the time was 'hunted' (the test score). All subjects were tested twice, 2-3 weeks apart; the OSA group after the commencement of CPAP. The Epworth Sleepiness Score (ESS) in patients was measured at the same visit. Results: The test score at visit 1 was 26.7% for normal subjects and 31.6% for patients with OSA. At visit 2, the test score was 25.0% for normal subjects and 29.9% for patients with OSA. The groups showed a small and identical improvement over the trial period in the test score, of 1.7% (p = 0.01 and p = 0.03 for the normal and OSA groups, respectively). The group with OSA experienced a drop in ESS of 7.5 (SD 5.5) points following treatment. Conclusion: The small and identical improvement in both groups suggests only a similar learning effect rather than any improvement due to reduced sleepiness. © 2013 S. Karger AG, Basel.
- Detection of Chronic Obstructive Pulmonary Disease in Primary Care in Salzburg, Austria: Findings from the Real World. [JOURNAL ARTICLE]
- Respiration 2013 Nov 28.
Background: Chronic obstructive pulmonary disease (COPD) is a major public health burden and profoundly affects individuals suffering from the disease. However, the majority of subjects with COPD are still undiagnosed. Objectives: To evaluate COPD prevalence and detection strategies for COPD in the primary-care setting. Methods: The study was conducted in a random sample of general practitioner (GP) offices in Salzburg (Austria). A questionnaire and post-bronchodilator (PBD) spirometry was administered to patients aged ≥40 years. Nonreversible airway obstruction was considered when PBD FEV1/FVC was <0.70. Severity of spirometrically defined COPD was graded according to the GOLD recommendations. Results: 60 GP offices were randomly selected for study participation, however only 30 (50.0%) were willing to participate. 1,230 of 9,820 (12.52%) patients consented to the protocol. Quality of PBD spirometry was evaluated, and 882 (71.7%) met ATS/ERS quality criteria. 7.5% (95% CI: 5.7-9.4%) of the patients had COPD grade II+ (FEV1/FVC <0.7 and FEV1 <80% of predicted), but only 22.4% of them reported a prior physician's diagnosis of COPD. Similar results were seen for the 2005 Salzburg BOLD (Burden of Obstructive Lung Disease) sample with regard to COPD GOLD II+ prevalence (10.7%) and proportion of underdiagnosis (82.3%). Conclusion: COPD in the primary-care setting is as prevalent and underdiagnosed as reported recently for the BOLD study. The surprisingly low participation rate of GPs and patients indicates that prevention of COPD is not a health priority, and that awareness for COPD has to heightened before case-finding strategies will be successful. © 2013 S. Karger AG, Basel.
- Optimization of Positive End-Expiratory Pressure by Volumetric Capnography Variables in Lavage-Induced Acute Lung Injury. [JOURNAL ARTICLE]
- Respiration 2013 Nov 28.
Background: In the acute respiratory distress syndrome (ARDS), lung-protective ventilation strategies combine the delivery of small tidal volumes (VT) with sufficient positive end-expiratory pressure (PEEP). However, an optimal approach guiding the setting of PEEP has not been defined. Monitoring volumetric capnography is useful to detect changes in lung aeration. Objectives: The aim of this study was to determine whether volumetric capnography may be a useful method to determine the optimal PEEP in ARDS. Methods: In 8 lung-lavaged piglets, PEEP was reduced from 20 to 4 cm H2O in steps of 4 cm H2O every 10 min followed by full lung recruitment. Volumetric capnography, respiratory mechanics, blood gas analysis, hemodynamic data and whole-lung computed tomography scans were obtained at each PEEP level. Results: After lung recruitment, end-expiratory lung volume progressively decreased from 1,160 ± 273 ml at PEEP 20 cm H2O to 314 ± 86 ml at PEEP 4 cm H2O. The ratio of alveolar dead space (VDalv) to alveolar VT (VTalv) and the phase III slope of volumetric capnography (SIII) reached a minimum at PEEP 16 cm H2O. At this PEEP level, overaerated lung regions were significantly reduced, nonaerated lung regions did not increase, and partial pressure of oxygen in arterial blood/fraction of inspired oxygen (P/F) and static respiratory system compliance (Crs) reached a maximum. At PEEP levels <16 cm H2O, nonaerated lung regions significantly increased, P/F and Crs deteriorated, and VDalv/VTalv and SIII began to increase. Conclusions: In this surfactant-depleted model, PEEP at the lowest VDalv/VTalv and SIII allows an optimal balance between lung overinflation and collapse. Hence, volumetric capnography is a useful bedside approach to identify the optimal PEEP. © 2013 S. Karger AG, Basel.
- What Proportion of Chronic Obstructive Pulmonary Disease Outpatients Is Eligible for Inclusion in Randomized Clinical Trials? [JOURNAL ARTICLE]
- Respiration 2013 Nov 20.
Background and Objective: We aimed to explore to what extent an unselected population of chronic obstructive pulmonary disease (COPD) outpatients would be eligible for inclusion in randomized clinical trials (RCTs). Methods: Retrospective analysis of the clinical records of outpatient subjects with an ascertained diagnosis of COPD. COPD outpatients were assessed against the following inclusion criteria: 40 < age < 80 years, current or former smokers, forced expiratory volume in the first second (FEV1) <70% predicted, no long-term oxygen therapy, no other concomitant lung diseases and absence of major extrapulmonary comorbidities. The study consisted of 2 phases; in phase 1, the criteria for inclusion in RCTs on COPD were selected, and in phase 2, the above criteria were applied to an unselected outpatient COPD population. Results: A total of 578 subjects (83% of the whole group) failed at least one of the inclusion criteria. Lung diseases other than COPD (occurring in 30% of our population, mostly bronchiectasis), long-term oxygen therapy (31%), FEV1 (19%), age (14%) and extrapulmonary comorbidities such as cognitive impairment (14%), arrhythmias (17%) and congestive heart disease (13%) would have been the most frequent causes for exclusion from RCTs. Conclusions: In real-life settings, more than 80% of COPD subjects are currently treated by protocols based on results of RCTs for which they would not have been eligible. We encourage a more extensive use of pragmatic trials in COPD to better modulate the application of results of RCTs to patients encountered in daily practice. © 2013 S. Karger AG, Basel.
- What We Talk about When We Talk about Randomized Controlled Trials. [JOURNAL ARTICLE]
- Respiration 2013 Nov 23.
- Complete Resolution of Cerebral Air Embolism Secondary to a Transbronchial Needle Aspiration. [JOURNAL ARTICLE]
- Respiration 2013 Nov 23.
Air embolism following transbronchial needle aspiration (TBNA) is extremely rare. To date, only 1 case has been described (estimated incidence: 0.02-0.07%). Here, a 70-year-old patient developed a left upper-lobe alveolar syndrome with no response to well-conducted antibiotic treatments. Conventional bronchoscopy was normal, but virtual bronchoscopy showed that the tumor was contiguous to the left B3-B4 division. During a second bronchoscopy, a TBNA was performed without bleeding, and pathology later revealed primitive lung adenocarcinoma. Immediately after the puncture, an epileptic seizure occurred with right rotation of the head and a tonic seizure of the left arm followed by left hemiplegia. A brain CT scan performed almost immediately showed no abnormalities and a chest radiography did not show any pleural or mediastinal aeric image. A few hours later, clonic seizures occurred and brain MRI showed lesions compatible with air embolisms (right gyral cortical location). Several hyperbaric therapy sessions successfully cured the neurological deficit. Despite its rarity, each practitioner of TBNA has to be aware of this side effect and its early treatment. The mechanism of such accidents remains unclear, but probably involves high bronchial pressure and venous trauma. © 2013 S. Karger AG, Basel.
- Pleural Effusions, Eosinophilia and a Positive Interferon-γ Release Assay. [JOURNAL ARTICLE]
- Respiration 2013 Nov 5.
- Baseline Predictors of Adherence to Positive Airway Pressure Therapy for Sleep Apnea: A 10-Year Single-Center Observational Cohort Study. [JOURNAL ARTICLE]
- Respiration 2013 Nov 5.
Background: Positive airway pressure (PAP) therapy is the standard treatment for obstructive sleep apnea syndrome (OSAS). Objectives: The aim of the current study was to determine operational long-term adherence to PAP and its predictors. Methods: In a retrospective single-center observational cohort study, we analyzed all patients referred to our center with suspected OSAS between November 2001 and November 2011. Baseline results and last follow-up data of each patient were analyzed. Kaplan-Meier estimates of adherence and Cox proportional hazard regression for age, gender, Epworth sleepiness scale (ESS) scores, body mass index, apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were performed. Evolution of adherence was analyzed in yearly cohorts comparing the proportion of patients discontinuing PAP within 6 and 12 months. Results: Of 4,638 referrals, 2,187 confirmed OSAS patients started PAP, 297 (14%) were referred out to other centers to follow-up, 42 (2%) died, and 92 (5%) no longer needed PAP. Of 1,756 patients, the median follow-up was 36 months [95% confidence interval (CI) 33.6-37.8], and adherence at 1, 5 and 10 years was 74 (CI 71-75; n = 1,028), 55 (CI 53-58; n = 281) and 51% (CI 48-55; n = 10), respectively. Adherence is associated with ESS score [hazard ratio (HR) 0.60; CI 0.47-0.78], ODI (HR 0.50; CI 0.32-0.77) and AHI (HR 0.56; CI 0.37-0.85). In yearly cohorts according to inclusion date, the absconder rate at 6 and 12 months was 20 (CI 18-22) and 27% (CI 25-30) for the first 8 years and improved to 10 (CI 7-15) and 14% (CI 10-19) for the last 2 years, respectively. Conclusions: Long-term adherence to PAP in OSAS is associated with baseline measures of disease severity. After 2009, an improvement in the adherence rate was observed. © 2013 S. Karger AG, Basel.