Probe-based confocal laser endomicroscopy of the respiratory tract: a data consistency analysis.

BACKGROUND: Probe-based confocal laser endomicroscopy is a novel imaging tool in the field of respiratory medicine. It enables a real-time and bedside qualitative characterization at the level of small airways but due to a relatively small field of view the reliability of quantification remains uncertain. METHODS: Twenty-six lung transplant recipients were subjected to two consecutive alveoloscopic imaging procedures within a median time interval of 90 days to analyze test-retest reliability. Only patients in a stable clinical condition were analyzed. We studied alveolar duct diameter, elastic fiber thickness at the alveolar level, the number of autofluorescent cells at the level of the alveolar space, the diameter of autofluorescent alveolar cells and their autofluorescence intensity. RESULTS: Intraclass correlation coefficients ranged from 0.56 for elastic fiber thickness, 0.62 for alveolar duct diameter, 0.29 for alveolar cell diameter, 0.74 for cellularity to 0.78 for alveolar cell autofluorescence. CONCLUSION: Probe-based confocal laser endomicroscopy enables imaging and quantitative measurements at the level of small airways and alveolar ducts. Test-retest reliability is good for cellularity and autofluorescence quantification but only moderate for morphometric analysis of elastic fibers and alveolar ducts.

Quality and reproducibility of spirometry in COPD patients in a randomized trial (UPLIFT®).

BACKGROUND: This study explores spirometry quality and reproducibility in the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT(®)) trial. METHODS: Four-year, randomized, double-blind, placebo-controlled, multicenter trial in 5993 patients with chronic obstructive pulmonary disease. Within-test variability of pre- and post-bronchodilator forced expiratory volume in 1 s (FEV(1)) was compared across study visits. Between-test variability of best pre- or post-FEV(1) values between two visits 6 months apart was compared at the start, middle and end of the trial. RESULTS: Three or more acceptable maneuvers were obtained in 93% of visits. Within-test variability of pre- and post-FEV(1) (mean standard deviation: 0.092 and 0.098 L) decreased during the trial. Between-test variability also decreased: pre-FEV(1) (visit 3-5 = 0.141 ± 0.138 L; visit 9-11 = 0.129 ± 0.121 L; visit 17-19 = 0.121 ± 0.122 L); post-FEV(1) (0.139 ± 0.140, 0.126 ± 0.123, 0.121 ± 0.122 L, respectively), and was dependent on age, sex, smoking status and disease stage, but not on bronchodilator response or study treatment. CONCLUSION: Spirometry quality in UPLIFT(®) was good and improved during the trial. Between-test variability across patient subgroups suggests that relevant cut-offs for individual disease monitoring are difficult to establish. TRIAL REGISTRATION NUMBER: NCT00144339.

Measurement validity of an electronic inspiratory loading device during a loaded breathing task in patients with COPD.

We studied the validity of a recently introduced, handheld, electronic loading device in providing automatically processed information on external inspiratory work, power and breathing pattern during loaded breathing tasks in patients with COPD. Thirty-five patients with moderate to severe COPD performed an endurance breathing task against a fixed resistive inspiratory load that corresponded to 55 ± 13% of their maximal inspiratory pressure. Flow and pressure signals during this task were sampled and processed at 500 Hz by the handheld loading device and at 100 Hz with an external, laboratory system that provided the "gold standard" reference data. Intra Class Correlations between methods were 0.97 for average mean inspiratory power, 0.98 for average mean pressure, 0.98 for average duty cycle, and 0.99 for total work (all p < 0.0001). We conclude that the handheld device provides automatically processed and valid estimates of physical units of energy during loaded breathing tasks. This enables health care providers to quantify the load on inspiratory muscles during these tests in daily clinical practice.

COPD awareness survey: do Belgian pulmonary physicians comply with the GOLD guidelines 2010?

Chronic Obstructive Pulmonary Disease (COPD) is underestimated, underdiagnosed and often under-treated in the general population. A survey of 17 structured questions, delivered to all Belgian pulmonary physicians (PPs) (116 responses), evaluated diagnosis and treatment strategies in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2010 and assessed opinions about the importance of diurnal variation of COPD symptoms. All COPD diagnoses (37% new cases) were spirometry confirmed. Main diagnostic parameters were symptoms (99%), external risk factors (99%), clinical examination (97%), exacerbations (96%) and patient mobility (96%). FEV1 (forced expiratory volume in 1s) (97%) or FEV1/FVC (ratio of FEV1 to forced vital capacity) (93%) were used most to assess diagnosis and severity. The 3 most important therapeutic objectives were symptom relief, preventing exacerbations, and improving quality of life; if these were not reached, the preferred strategy (60% of PPs) was adding another medication. Treatment strategies varied with COPD stage: short-acting beta2-agonists (90%) and short-acting anti-cholinergics (59%) were used for GOLD I disease, whereas for higher stages long-acting beta2-agonists (36-48%) and long-acting anti-cholinergics (79%) were given with inhaled corticosteroids (21-67%). Symptoms were perceived to vary throughout the day, affecting quality of life (97%) and mobility (89%). In particular, respiratory symptoms were more severe in the morning (51-92%), leading PPs to adapt treatment (69%). This survey demonstrated that management of COPD by PPs in Belgium is generally in line with the GOLD guidelines 2010 and that they perceive morning symptoms as being frequent and having an impact on patient's life.

Diaphragm plication for unilateral diaphragm paralysis: a case report and review of the literature.

Unilateral diaphragm paralysis is an often not recognised cause of dyspnoea. We present a patient with a unilateral phrenic nerve paralysis treated with diaphragmatic plication. Patient presented with life-style limiting dyspnoea and pulmonary function showed a decrease in FVC when lying down. Since there was no improvement after respiratory muscle training, plication of the hemidiaphragm was performed by a small thoracotomy. The patient improved with regard to respiratory complaints and lung function. Furthermore, we also demonstrate for the first time a significant improvement in exercise capacity with accompanying striking amelioration of quality of life. The patient is now in follow up up for more than 2 years and the impressive improvement in exercise capacity remains present. Surgical treatment of unilateral diaphragm paralysis has been described in case reports and in small series since 1985. Although comparison of the available data is difficult a diaphragm plication seems an effective and safe procedure for patients with symptomatic, acquired unilateral diaphragm paralysis. Improvement of dyspnoea is present in the majority of patients and we even observed an impressive amelioration in exercise capacity. Consequently, it seems appropriate to propose plication to patients with clear symptoms from the moment spontaneous recovery seems unlikely; yet, prospective randomised controlled studies are needed to prove this.

Exercise training after lung transplantation improves participation in daily activity: a randomized controlled trial.

The effects of exercise training after lung transplantation have not been studied in a randomized controlled trial so far. We investigated whether 3 months of supervised training, initiated immediately after hospital discharge, improve functional recovery and cardiovascular morbidity of patients up to 1 year after lung transplantation. Patients older than 40 years, who experienced an uncomplicated postoperative period, were eligible for this single blind, parallel group study. Sealed envelopes were used to randomly allocate patients to 3 months of exercise training (n = 21) or a control intervention (n = 19). Minutes of daily walking time (primary outcome), physical fitness, quality of life and cardiovascular morbidity were compared between groups adjusting for baseline assessments in a mixed models analysis. After 1 year daily walking time in the treated patients (n = 18) was 85 ± 27 min and in the control group (n = 16) 54 ± 30 min (adjusted difference 26 min [95%CI 8-45 min, p = 0.006]). Quadriceps force (p = 0.001), 6-minute walking distance (p = 0.002) and self-reported physical functioning (p = 0.039) were significantly higher in the intervention group. Average 24 h ambulatory blood pressures were significantly lower in the treated patients (p ≤ 0.01). Based on these results patients should be strongly encouraged to participate in an exercise training intervention after lung transplantation.

Determinants of physical activity in daily life in candidates for lung transplantation.

BACKGROUND: Participation in daily physical activity (PA) has never been objectively assessed in candidates for lung transplantation (LTx). The main research questions were: 1) How active are LTx-candidates in daily life? 2) What are determinants of activity behavior before LTX? METHODS: Ninety-six candidates for LTx (diagnosis of COPD or interstitial lung disease; mean age 55 ± 7 years) underwent measurements of PA, pulmonary function, 6-min walking distance (6MWD), muscle force and health-status (SF-36 scale). RESULTS: Patients were markedly inactive (5% of waking hours walking, 26% standing and 69% sedentary). Backward multiple regression identified 6MWD (expressed as % of predicted value; ß = 73.0 steps, partial r(2) = 0.36, p = 0.00), a higher score on the energy/fatigue scale of the SF-36 (ß = 28.6 steps, partial r(2) = 0.09, p = 0.00) and a higher expiratory muscle force (expressed as % of predicted value; ß = 11.8 steps, partial r(2) = 0.05, p = 0.02) as determinants of daily steps. Minutes of mild to moderate (≥2 METs) activity were determined by 6MWD (expressed as % of predicted value; ß = 2.14 min, partial r(2) = 0.30, p = 0.00), inspiratory muscle force (expressed as % of predicted value; ß = 0.33 min, partial r(2) = 0.04, p = 0.05) and seasonal influences (spring/summer vs. autumn/winter: ß = 18.95 min, partial r(2) = 0.04, p = 0.05). The overall fit of the models was r(2) = 0.50 and r(2) = 0.38, respectively. CONCLUSIONS: The 6MWD was the main determinant of an inactive lifestyle in these patients. Respiratory muscle force, energy and fatigue and seasonal variations explained some additional variability in activity behavior. Patients should be encouraged to participate in interventions aimed at improving physical fitness and participation in daily physical activity before LTx.

Accuracy of office spirometry performed by trained primary-care physicians using the MIR Spirobank hand-held spirometer.

BACKGROUND: With the availability of compact, portable, effective microspirometers, pulmonary function tests no longer need to be performed only in specialized laboratories. However, the perception persists that small flow-sensing devices are less accurate than volume-sensing spirometers. OBJECTIVES: To study the accuracy of spirometry performed with the MIR Spirobank® and to investigate how accurately trained primary-care physicians can perform spirometry using a portable electronic spirometer. METHODS: Patients with suspected occupational asthma were submitted to specific bronchial challenge tests in the pulmonary function laboratory according to published recommendations. Serial measurements were performed with the Jaeger MasterScope device (reference standard) or the Spirobank device. Data were generated from 908 parallel measurements on 34 patients. Furthermore, 16 patients with documented moderate to severe COPD were examined in a carousel set-up by four trained physicians who each used his/her own Spirobank device coupled to a laptop computer. RESULTS: The Spirobank spirometer performed very well compared with the Jaeger MasterScope in a laboratory environment, displaying an underestimation of the forced expiratory volume in 1 s (FEV(1)) and FEV(1)/forced vital capacity (FVC) of 2-5%. High correlations were found for the pulmonary function parameters. The highest correlation was for FEV(1) (r(2) = 0.949) and the lowest for the maximum expiratory flow at 25% of FVC (MEF(25)) (r(2) = 0.864). Only 2% of the observed variation in the measurement results could be explained by the type of device. CONCLUSIONS: The Spirobank device seems to be appropriate for research purposes if the standardized protocol is used correctly and the acceptability criteria are respected.

Rehabilitation and acute exacerbations.

Recent evidence indicates that acute exacerbations of chronic obstructive pulmonary disease aggravate the extrapulmonary consequences of the disease. Skeletal muscle dysfunction, a sustained decrease in exercise tolerance, enhanced symptoms of depression and fatigue are reported. Avoidance of physical activities is likely to be a key underlying mechanism and increases the risk of new exacerbations. Pulmonary rehabilitation is an intervention targeting these systemic consequences. Exercise strategies need to be adapted to the increased feelings of dyspnoea and fatigue. This review aims to describe the systemic consequences of acute exacerbations and compiles evidence for the feasibility and effectiveness of different rehabilitation strategies to counteract these consequences during and/or immediately after the acute phase of the exacerbation. Resistance training and neuromuscular electrical stimulation have been applied safely in frail, hospitalised patients and have the potential to prevent muscle atrophy. Comprehensive pulmonary rehabilitation, including general exercise training, can be implemented immediately after the exacerbation, leading to a reduction in hospital admissions and an increase in exercise tolerance and quality of life. Self-management strategies play a crucial role in changing disease-related health behaviour and preventing hospital admissions.

Impact of care pathways for in-hospital management of COPD exacerbation: a systematic review.

BACKGROUND: In-hospital management of COPD exacerbation is suboptimal, and outcomes are poor. Care pathways are a possible strategy for optimizing care processes and outcomes. OBJECTIVES: The aim of the literature review was to explore characteristics of existing care pathways for in-hospital management of COPD exacerbations and to address their impact on performance of care processes, clinical outcomes, and team functioning. METHODS: A literature search was conducted for articles published between 1990 and 2010 in the electronic databases of Medline, CINAHL, EMBASE, and Cochrane Library. Main inclusion criteria were (I) patients hospitalized for a COPD exacerbation; (II) implementation and evaluation of a care pathway; (III) report of original research, including experimental and quasi experimental designs, variance analysis, and interviews of professionals and patients about their perception on pathway effectiveness. RESULTS: Four studies with a quasi experimental design were included. Three studies used a pre-post test design; the fourth study was a non randomized controlled trial comparing an experimental group where patients were treated according to a care pathway with a control group where usual care was provided. The four studied care pathways were multidisciplinary structured care plans, outlining time-specific clinical interventions and responsibilities by discipline. Statistic analyses were rarely performed, and the trials used very divergent indicators to evaluate the impact of the care pathways. The studies described positive effects on blood sampling, daily weight measurement, arterial blood gas measurement, referral to rehabilitation, feelings of anxiety, length of stay, readmission, and in-hospital mortality. CONCLUSIONS: Research on COPD care pathways is very limited. The studies described few positive effects of the care pathways on diagnostic processes and on clinical outcomes. Though due to limited statistical analysis and weak design of the studies, the internal validity of results is limited. Therefore, based on these studies the impact of care pathways on COPD exacerbation is inconclusive. These findings indicate the need for properly designed research like a cluster randomized controlled trial to evaluate the impact of COPD care pathways on performance of care processes, clinical outcomes, and teamwork.

The TERT-CLPTM1L locus for lung cancer predisposes to bronchial obstruction and emphysema.

Clinical studies suggest that bronchial obstruction and emphysema increase susceptibility to lung cancer. We assessed the possibility of a common genetic origin and investigated whether the lung cancer susceptibility locus on chromosome 5p15.33 increases the risk for bronchial obstruction and emphysema. Three variants in the 5p15.33 locus encompassing the TERT and CLPTM1L genes were genotyped in 777 heavy smokers and 212 lung cancer patients. Participants underwent pulmonary function tests and computed tomography of the chest, and completed questionnaires assessing smoking behaviour. The rs31489 C-allele correlated with reduced forced expiratory volume in 1 s (p=0.006). Homozygous carriers of the rs31489 C-allele exhibited increased susceptibility to bronchial obstruction (OR 1.82, 95% CI 1.24-2.69; p=0.002). A similar association was observed for diffusing capacity of the lung for carbon monoxide (p=0.004). Consistent with this, CC-carriers had an increased risk of emphysema (OR 2.04, 95% CI 1.41-2.94; p=1.73 × 10(-4)) and displayed greater alveolar destruction. Finally, CC-carriers also had an increased risk for lung cancer (OR 1.90, 95% CI 1.21-2.99; p=0.005), and were more susceptible to developing both lung cancer and bronchial obstruction than lung cancer alone (OR 2.11, 95% CI 1.04-4.26; p=0.038). The rs31489 variant on 5p15.33 is associated with bronchial obstruction, presence and severity of emphysema, and lung cancer.

(Ex-)smoking asthma patients in general and specialized Belgian practice.

INTRODUCTION: Smokers are often excluded from asthma studies. In the present study, data are presented on the prevalence, characteristics and management approach of this patient population in the Belgian practice both at the level of general practitioners (GPs) and specialists. MATERIALS AND METHODS: One hundred and nineteen smoking, non-smoking and ex-smoking patients (25-65 yrs) with asthma, COPD or both, were recruited by 33 GPs and 33 specialists. Data were obtained retrospectively from medical records. However, only a small number of files were complete. RESULTS: The majority of COPD patients were (ex-)smokers: 94% in the specialist group, 78% in the GP group. Cardiovascular comorbidity appeared in both groups in the same frequency order: COPD>(ex-)smoking patients with asthma (AS)>non-smoking patients with asthma (ANS), with a significant difference between AS and ANS in the specialist population. Chronic cough during more than 3 months in two consecutive years was reported in 97% of COPD patients, in 71% of the AS patients and in only 25% of the ANS patients. The type of cough differed between AS and ANS in the GP group, with a higher prevalence of productive cough in the former. Treatment patterns observed were as expected according to diagnosis except for a disproportionate use of Tiotropium in AS in the GP group. CONCLUSION: AS were somewhere in between COPD patients and ANS for a large number of the characteristics studied, suggesting that they are an intermediate phenotype between COPD and asthma.

Impact of inspiratory muscle training in patients with COPD: what is the evidence?

A meta-analysis including 32 randomised controlled trials on the effects of inspiratory muscle training (IMT) in chronic obstructive pulmonary disease (COPD) patients was performed. Overall and subgroup analyses with respect to training modality (strength or endurance training, added to general exercise training) and patient characteristics were performed. Significant improvements were found in maximal inspiratory muscle strength (P(I,max); +13 cmH2O), endurance time (+261 s), 6- or 12-min walking distance (+32 and +85 m respectively) and quality of life (+3.8 units). Dyspnoea was significantly reduced (Borg score -0.9 point; Transitional Dyspnoea Index +2.8 units). Endurance exercise capacity tended to improve, while no effects on maximal exercise capacity were found. Respiratory muscle endurance training revealed no significant effect on P(I,max), functional exercise capacity and dyspnoea. IMT added to a general exercise programme improved P(I,max) significantly, while functional exercise capacity tended to increase in patients with inspiratory muscle weakness (P(I,max) <60 cmH2O). IMT improves inspiratory muscle strength and endurance, functional exercise capacity, dyspnoea and quality of life. Inspiratory muscle endurance training was shown to be less effective than respiratory muscle strength training. In patients with inspiratory muscle weakness, the addition of IMT to a general exercise training program improved P(I,max) and tended to improve exercise performance.

[COPD and bone metabolism: a clinical update]. / BPCO et métabolisme osseux: une mise à jour clinique.

Increasing evidence indicates that COPD and osteoporosis are strongly linked. Both diseases share common risk factors like age, smoking and inactivity but the typical presence in COPD of systemic inflammation, vitamin D deficiency and the frequent use of corticosteroids catalyse ongoing bone resorption. Osteoporosis in its turn may lead to vertebral compression fractures with a consequent further decline of forced vital capacity and forced expiratory volume in one second. In addition, fragility fractures in disabled COPD patients may cause further immobility and increased morbidity. Prevention and treatment of osteoporosis in COPD should therefore be based on population specific risk assessments which combine measures of bone mineral density and clinical factors. Unfortunately, intervention studies specifically designed for patients with COPD are currently lacking and no specific guidelines have yet been established. Hence, a rigorous application of the current treatment guidelines with respect to osteoporosis in general would already be a major step forward in the treatment of COPD.