Baseline dependent minimally important differences for clinical outcomes of pulmonary rehabilitation in people with COPD.

INTRODUCTION: Minimally important differences (MIDs) for common outcomes of pulmonary rehabilitation are well documented for people with chronic obstructive pulmonary disease (COPD). It is not known whether MIDs differ based on COPD disease characteristics. This study aimed to estimate MIDs for clinical outcomes of pulmonary rehabilitation dependent upon baseline characteristics. METHODS: A database containing 2791 people with COPD was split into derivation (n=2245; age 66±9 years; 50% males; FEV1 47±20% predicted) and comparator (n=546; age 66±9 years; 47% males; FEV1 46±21% predicted) cohorts. MIDs were estimated using 0.5 x SD (symmetrically distributed) or 0.5 x IQR (non-symmetrically distributed) for: 6-minute walk test (6MWT), constant work rate test (CWRT), COPD assessment test (CAT), St. George's respiratory questionnaire (SGRQ), hospital anxiety and depression scale (HADS), and fat-free mass index (FFMI). MIDs were estimated based on baseline outcome scores, lung function, modified medical research council (mMRC) grade and FFMI. RESULTS: MID estimates were comparable to previously reported values. MIDs for SGRQ domains (Symptom=8.7 points, Activity=7.1 points, Impact=8.1 points) and FFMI were produced (0.36kg/m2). There was greater variation of change in 6MWT, SGRQ-activity, SGRQ-impact, HADS and FFMI on which the MIDs were determined when categorising for baseline values (all, p<0.05). Greater variation of change in 6MWT on which the MIDs were determined was evident with COPD disease severity grouping (p<0.05). The magnitude of change in 6MWT, CAT, CWRT, SGRQ-activity, and FFMI with baseline mMRC score categorisation resulted in greater variation on which the MIDs were determined (all, p<0.05). Baseline stratification for FFMI resulted in greater variation of change in CWRT (p<0.001) and HADS-depression (p = 0.043) on which MIDs were determined. DISCUSSION: Findings suggest that baseline presentation should be considered for people with COPD when assessing the efficacy of pulmonary rehabilitation. However, clinical significance of the variation underpinning MIDs is yet to be determined.

Distribution of chronic cough phenotypes in the general population: A cross-sectional analysis of the LEAD cohort in Austria.

RATIONALE: Recent guidelines consider chronic cough to be a unique clinical entity with different phenotypes. We aimed to investigate them in a general population and to describe prevalence, distribution, and characteristics of these phenotypes within the Austrian general population. METHODS: From the LEAD study, a longitudinal observational population-based cohort, data from questionnaires and spirometry of 10,057 adult participants was analysed. Chronic cough was defined as coughing nearly every day during the last 12 months for at least 3 months (>12 weeks). RESULTS: The prevalence of chronic cough was 9% and increased with age. We found no sex predominance but a female preponderance (68%) in never smokers. A presumable cause was identified in 85% of which more than half (53.9%) had two phenotypes, 36.9% belonged to one only and 9.2% to three or more. Regarding the distribution of phenotypes, 40.8% were current smokers, 32.6% had an ACE inhibitor intake, 18.2% GERD, 17.6% asthmatic cough, 9.7% UACS and 28.3% other diseases associated with chronic cough. 15% had unexplained chronic cough with no identifiable phenotype. Current smoking, low socioeconomic status, obesity, COPD and obstructive sleep apnea were associated factors with chronic cough. CONCLUSION: Chronic cough is common among adults in Austria and highly prevalent in the older population. Most participants can be phenotyped with simple questionnaire-based assessment and can therefore potentially receive specific treatment without intensive clinical workup.

Comorbidity clusters in patients with moderate-to-severe OSA.

PURPOSE: Obstructive sleep apnea (OSA) is a prevalent and multifaceted disease. To date, the presence and severity of objectively identified comorbidities and their association with specific OSA phenotypes, CPAP adherence, and survival remain to be elucidated. The aim of this study is to cluster patients with OSA based on 10 clinically important objectively identified comorbidities, and to characterize the comorbidity clusters in terms of clinical and polysomnographic characteristics, CPAP adherence, and survival. STUDY DESIGN AND METHODS: Seven hundred ten consecutive patients starting CPAP for moderate-to-severe OSA were included. Comorbidities were based on generally accepted cutoffs identified in the peer-reviewed literature. Self-organizing maps were used to order patients based on presence and severity of their comorbidities and to generate clusters. RESULTS: The majority of patients were men (80%). They were generally middle-aged (52 years) and obese (BMI: 31.5 kg/m2). Mean apnea-hypopnea index (AHI) was 41 ± 20 per h of sleep. More than 94% of the patients had one or more comorbidities with arterial hypertension, dyslipidemia, and obesity being the most prevalent. Nine comorbidity clusters were identified. The clinical relevance of these comorbidity clusters was highlighted by the difference in symptoms, PSG parameters, and cardiovascular risk. Also, differences in CPAP adherence, improvements in ESS, and long-term survival were present between the clusters. CONCLUSION: Comorbidity prevalence in patients with OSA is high, and different comorbidity clusters, demonstrating differences in cardiovascular risk, CPAP adherence, and survival, can be identified. These results further substantiate the need for a comprehensive assessment of patients with OSA beyond the AHI.

Associations between bone attenuation and prevalent vertebral fractures on chest CT scans differ with vertebral fracture locations.

Vertebral fracture (VF) locations are bimodally distributed in the spine. The association between VF and bone attenuation (BA) measured on chest CT scans varied according to the location of VFs, indicating that other factors than only BA play a role in the bimodal distribution of VFs. INTRODUCTION: Vertebral fractures (VFs) are associated with low bone mineral density but are not equally distributed throughout the spine and occur most commonly at T7-T8 and T11-T12 ("cVFs") and less commonly at T4-T6 and T9-T10 ("lcVF"). We aimed to determine whether associations between bone attenuation (BA) and VFs vary between subjects with cVFs only, with lcVFs only and with both cVFs and lcVFs. METHODS: Chest CT images of T4-T12 in 1237 smokers with and without COPD were analysed for prevalent VFs according to the method described by Genant (11,133 vertebrae). BA (expressed in Hounsfield units) was measured in all non-fractured vertebrae (available for 10,489 vertebrae). Linear regression was used to compare mean BA, and logistic regression was used to estimate the association of BA with prevalent VFs (adjusted for age and sex). RESULTS: On vertebral level, the proportion of cVFs was significantly higher than of lcVF (5.6% vs 2.0%). Compared to subjects without VFs, BA was 15% lower in subjects with cVFs (p < 0.0001), 25% lower in subjects with lcVFs (p < 0.0001) and lowest in subjects with cVFs and lcVFs (- 32%, p < 0.0001). The highest ORs for presence of VFs per - 1SD BA per vertebra were found in subjects with both cVFs and lcVFs (3.8 to 4.6). CONCLUSIONS: The association between VFs and BA differed according to VF location. ORs increased from subjects with cVFs to subjects with lcVFs and were highest in subjects with cVFs and lcVFs, indicating that other factors than only BA play a role in the bimodal VF distribution. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00292552.

Association between vertebral fractures and coronary artery calcification in current and former smokers in the ECLIPSE cohort.

In smokers and former smokers from the ECLIPSE cohort, there is an association between prevalent vertebral fractures (VFs) and coronary artery calcification (CAC). Chest CT scans provide the opportunity to evaluate VFs and CAC, which are potentially important comorbidities, each of which is amenable to effective interventions. INTRODUCTION: Prevalence of VFs among smokers and patients with chronic obstructive pulmonary disease (COPD) is high, and an association between CAC and osteoporosis has been described. We investigated the associations between VFs and CAC (expressed in Agatston score) in (former) smokers. METHODS: Current and former smokers from the ECLIPSE study (designed to determine underlying COPD progression mechanisms) were studied. Baseline Agatston score (zero (0), medium (1-400), or high (> 400)), baseline bone attenuation (BA), and prevalent and incident VFs (vertebrae T1-L1) were assessed on CT. RESULTS: A total of 586 subjects were included (mean age 59.8 ± 8.3; 62.3% men; 70.1% with COPD; 21.0% with prevalent VFs; 196 with zero, 266 with medium, and 124 with high Agatston score). Of these, 23.4% suffered incident VFs within 3 years. In multivariate models, prevalent VFs were associated with medium (1.83 [95% CI 1.01-3.30]) and with high (OR = 3.06 [1.45-6.47]) Agatston score. After adjustment for BA, prevalent VFs were still associated with high (OR = 2.47 [1.13-5.40]), but not significantly with medium Agatston score (OR = 1.57 [0.85-2.88]). Similarly, after adjustment for BA, high (OR = 2.06 [1.02-4.13]) but not medium Agatston score (OR = 1.61 [0.88-2.94]) was associated with prevalent VFs. Agatston score at baseline was not associated with short-term VF incidence. CONCLUSION: In (former) smokers, there was an association between prevalent VFs and Agatston score. Chest CT scans provide the opportunity to also evaluate for VFs and CAC, which are potentially important comorbidities, each of which is amenable to effective interventions.

Vertebral bone attenuation in Hounsfield Units and prevalent vertebral fractures are associated with the short-term risk of vertebral fractures in current and ex-smokers with and without COPD: a 3-year chest CT follow-up study.

CT scans performed to evaluate chronic obstructive pulmonary disease (COPD) also enable evaluation of bone attenuation (BA; a measure of bone density) and vertebral fractures (VFs). In 1239 current/former smokers with (n = 999) and without (n = 240) COPD, the combination of BA and prevalent VFs was associated with the incident VF risk. INTRODUCTION: Chest CT scans are increasingly used to evaluate pulmonary diseases, including COPD. COPD patients have increased risk of osteoporosis and VFs. BA on CT scans is correlated with bone mineral density and prevalent VFs. The aim of this study was to evaluate the association between BA and prevalent VFs on chest CT scans, and the risk of incident VFs in current and former smokers with and without COPD. METHODS: In participants of the ECLIPSE study with baseline and 1-year and 3-year follow-up CT scans, we evaluated BA in vertebrae T4-T12 and prevalent and incident VFs. RESULTS: A total of 1239 subjects were included (mean age 61.3 ± 8.0, 61.1% men, 999 (80.6%) COPD patients). The mean BA was 155.6 ± 47.5 Hounsfield Units (HU); 253 (20.5%) had a prevalent VF and 296 (23.9%) sustained an incident VF within 3 years. BA and prevalent VFs were associated with incident VFs within 1 (per - 1SD HR = 1.38 [1.08-1.76] and HR = 3.97 [2.65-5.93] resp.) and 3 years (per - 1SD HR = 1.25 [1.08-1.45] and HR = 3.10 [2.41-3.99] resp.), while age, sex, body mass index (BMI), smoking status and history, or presence of COPD was not. In subjects without prevalent VFs and BA, and for 1-year incidence, BMI values were associated with incident fractures (1 year, BA per - 1SD HR = 1.52 [1.05-2.19], BMI per SD HR = 1.54 [1.13-2.11]; 3 years, per - 1SD HR = 1.37 [1.12-1.68]). CONCLUSIONS: On CT scans performed for pulmonary evaluation in (former) smokers with and without COPD, the combination of BA and prevalent VFs was strongly associated with the short-term risk of incident VFs.

Impact of pulmonary rehabilitation on activities of daily living in patients with chronic obstructive pulmonary disease.

A high proportion of patients with chronic obstructive pulmonary disease (COPD) experience problems during the performance of activities of daily living (ADLs). We aimed to determine the effects of a comprehensive 8-wk pulmonary rehabilitation program on the physiologic response to and performance of ADLs in patients with COPD. Before and after pulmonary rehabilitation, 31 patients with COPD [71% men; mean age: 64.2 (SD 8.4) years; mean forced expiratory volume in the first second: 54.6 (SD 19.9) % predicted] performed physical function tests, the Canadian Occupational Performance Measure (COPM), and an ADL test consisting of the following: putting on socks, shoes, and vest; stair climbing; washing up four dishes, cups, and saucers; doing groceries and putting away groceries in a cupboard; folding eight towels; and vacuum cleaning for 4 min. Metabolic load, ventilation, and dynamic hyperinflation were assessed using an Oxycon mobile device. In addition, symptoms of dyspnea and fatigue and time to complete ADLs were recorded. After rehabilitation, patients with COPD used a significantly lower proportion of their peak aerobic capacity and ventilation to perform ADLs, accompanied by lower Borg scores for dyspnea and fatigue. Furthermore, patients needed significantly less time to complete ADLs. Dynamic hyperinflation occurred during the performance of ADLs, which did not change following pulmonary rehabilitation. Changes in physical function, including six-min walk distance, constant work rate test, quadriceps muscle strength, and COPM were significantly correlated with change in average total oxygen uptake during the performance of the ADL test. A comprehensive pulmonary rehabilitation program can improve the physiologic response to and actual performance of ADLs in patients with COPD. NEW & NOTEWORTHY A high proportion of patients with chronic obstructive pulmonary disease (COPD) experience problems during the performance of activities of daily living (ADLs). This study clearly demonstrated that a comprehensive pulmonary rehabilitation program can improve the performance of ADLs in patients with COPD, indicated by a significantly shorter time to perform ADLs and a lower metabolic load and dyspnea sensation.

Diagnosis of vertebral deformities on chest CT and DXA compared to routine lateral thoracic spine X-ray.

X-ray, CT and DXA enable diagnosis of vertebral deformities. For this study, level of agreement of vertebral deformity diagnosis was analysed. We showed that especially on subject level, these imaging techniques could be used for opportunistic screening of vertebral deformities in COPD patients. INTRODUCTION: X-ray and CT are frequently used for pulmonary evaluation in patients with chronic obstructive pulmonary disease (COPD) and also enable to diagnose vertebral deformities together with dual-energy X-ray absorptiometry (DXA) imaging. The aim of this research was to study the level of agreement of these imaging modalities for diagnosis of vertebral deformities from T4 to L1. METHODS: Eighty-seven subjects (mean age of 65; 50 males; 57 COPD patients) who had X-ray, chest CT (CCT) and DXA were included. Evaluable vertebrae were scored twice using SpineAnalyzer™ software. ICCs and kappas were calculated to examine intra-observer variability. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUROC) were calculated to compare vertebral deformities diagnosed on the different imaging modalities. RESULTS: ICCs for height measurements were excellent (> 0.94). Kappas were good to excellent (0.64-0.77). At vertebral level, the AUROC was 0.85 for CCT vs. X-ray, 0.74 for DXA vs. X-ray and 0.77 for DXA vs. CCT. Sensitivity (51%-73%) and PPV (57%-70%) were fair to good; specificity and NPV were excellent (≥ 96%). At subject level, the AUROC values were comparable. CONCLUSIONS: Reproducibility of height measurements of vertebrae is excellent with all three imaging modalities. On subject level, diagnostic performance of CT (PPV 79-82%; NPV 90-93%), and to a slightly lesser extend of DXA (PPV 73-77%; NPV 80-89%), indicates that these imaging techniques could be used for opportunistic screening of vertebral deformities in COPD patients.

Use of systemic glucocorticoids and the risk of major osteoporotic fractures in patients with sarcoidosis.

This study revealed the risk of major osteoporotic fracture in patients with sarcoidosis exposed to glucocorticoids. Current use of glucocorticoids was associated with a risk of fracture, with no difference between patients with and without sarcoidosis. Sarcoidosis per se was not associated with an increased fracture risk. INTRODUCTION: Sarcoidosis is a multi-organ, chronic inflammatory, granulomatous disorder that most frequently affects the lungs, lymph nodes, skin, eyes, and liver, but may occur in any organ, including the bones. While oral glucocorticoids (GCs) are commonly used as initial treatment, little is known about the risk of major osteoporotic fractures in patients with sarcoidosis exposed to GCs. METHODS: A case-control study was conducted using the Danish National Hospital Discharge Registry (NHDR) between January 1995 and December 2011. Conditional logistics regression models were used to derive adjusted odds ratios (OR) of major osteoporotic fractures in subjects with and without sarcoidosis stratified by average daily and cumulative dose exposures. RESULTS: A total of 376,858 subjects with a major osteoporotic fracture and the same number of subjects without this event were identified (mean age 64.2 ± 19.5 years, 69% female). In patients with sarcoidosis (n = 124), current use of GC was associated with an increased risk of major osteoporotic fracture (adjusted (adj.) OR 1.74; 95% CI 1.17-2.58), which dropped to baseline levels after discontinuation. In subjects without sarcoidosis, this risk was comparable (adj. OR 1.36; 95% CI 1.32-1.40). In sarcoidosis patients, cumulative dose 1.0-4.9 g and >10 g prednisolone equivalents were associated with increased risk of major osteoporotic fracture (adj. OR 2.75; 95% CI 1.06-7.14 and 2.22; 95% CI 1.17-4.22, respectively), whereas a cumulative dose of <1.0 g and 5.0-9.9 g was not associated with major osteoporotic fracture risk. CONCLUSION: Both in subjects with and without sarcoidosis, current expose to GC is associated with increased risk of major osteoporotic fractures, with no between-group difference. Sarcoidosis per se was not associated with increased fracture risk. Having sarcoidosis per se, i.e., if not treated with GC, is not a risk factor for fracture, and such patients may only need risk assessment when they commence GC therapy.

Personalized medicine and chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: The current review summarizes ongoing developments in personalized medicine and precision medicine in chronic obstructive pulmonary disease (COPD). Our current approach is far away of personalized management algorithms as current recommendations for COPD are largely based on a reductionist disease description, operationally defined by results of spirometry. RECENT FINDINGS: Besides precision medicine developments, a personalized medicine approach in COPD is described based on a holistic approach of the patient and considering illness as the consequence of dynamic interactions within and between multiple interacting and self-adjusting systems. Pulmonary rehabilitation is described as a model of personalized medicine. Largely based on current understanding of inflammatory processes in COPD, targeted interventions in COPD are reviewed. Augmentation therapy for α-1-antitrypsine deficiency is described as model of precision medicine in COPD based in profound understanding of the related genetic endotype. SUMMARY: Future developments of precision medicine in COPD require identification of relevant endotypes combined with proper identification of phenotypes involved in the complex and heterogeneous manifestations of COPD.

[Two sisters with lung emphysema]. / Twee zussen met longemfyseem.

BACKGROUND: α1-antitrypsin is an antiprotease that is mainly produced in the liver; it plays a crucial role in the protection of lung parenchyma against the destructive effects of proteases. Mutations in the α1-antitrypsin gene can cause α1-antitrypsin deficiency. Individuals homozygous for the Z-genotype have drastically lowered serum α1-antitrypsine concentrations and often develop lung emphysema at an early age. CASE DESCRIPTION: A 38-year-old woman and her 43-year-old sister both developed lung emphysema at an early age; this could be attributed to severe α1-antitrypsin deficiency. The only treatment for this condition is α1-antitrypsin supplement therapy, but this therapy is not reimbursed by health insurance companies in the Netherlands. CONCLUSION: α1-antitrypsin deficiency is a relatively rare cause of lung emphysema and can be seen as an orphan phenotype of chronic obstructive pulmonary disease (COPD). We appeal for reconsideration of coverage of α1-antitrypsine supplement therapy by basic health insurance in the Netherlands, on the basis of a recent randomised placebo-controlled study in which the protective effect of this therapy on progressive emphysema was demonstrated by CT lung densitometry.

Relationship between pulmonary rehabilitation and care dependency in COPD.

The aims of this study were to explore care dependency before and after pulmonary rehabilitation (PR) in patients with COPD (n=331) and to compare the response to PR between care dependent and independent patients. At baseline, 85 (25.7%) patients had a Care Dependency Scale (CDS) score ≤68 points and were considered as care dependent. CDS scores of these patients improved after PR (p<0.001). After PR, CDS score of 38 (44.7%) patients with a baseline CDS score ≤68 points increased to >68 points. Patients with a baseline CDS score ≤68 points or >68 points showed after PR a comparable improvement in COPD Assessment Test, Hospital Anxiety and Depression Scale and 6-min walk distance (all p<0.05). TRIAL REGISTRATION NUMBER: NTR3416 (The Netherlands).

Prevalence of thoracic pain in patients with chronic obstructive pulmonary disease and relationship with patient characteristics: a cross-sectional observational study.

BACKGROUND: Objectives of this study were to evaluate the prevalence of thoracic pain in patients with chronic obstructive pulmonary disease (COPD) and its relationship with Forced Expiratory Volume in the first second (FEV1), static hyperinflation, dyspnoea, functional exercise capacity, disease-specific health status, anxiety, and depression. METHODS: This cross-sectional observational study included patients with COPD entering pulmonary rehabilitation. Participants underwent spirometry, plethysmography, and measurement of single breath diffusion capacity. Pain was assessed using a multidimensional, structured pain interview. In addition, dyspnoea severity (Modified Medical Research Council Dyspnoea Scale (mMRC)), functional exercise capacity (six-minute walking distance (6MWD)), disease-specific health status (COPD Assessment Test (CAT)), and symptoms of anxiety and depression (Hospital Anxiety Depression Scale (HADS)) were recorded. RESULTS: 55 of the included 67 participants reported chronic pain (82.1%). 53.7% had thoracic pain. After considering multiple comparisons, only younger age and worse CAT scores were related with the presence of thoracic pain (p = 0.01). There were no relationships between thoracic pain and FEV1, static lung hyperinflation, diffusion capacity, mMRC score, 6MWD, anxiety or depression. CONCLUSION: Thoracic pain is highly prevalent in COPD patients and is related to impaired disease-specific health status, but there is no relationship with FEV1, static hyperinflation, dyspnoea severity or functional exercise capacity.

A randomized controlled trial on the benefits and respiratory adverse effects of morphine for refractory dyspnea in patients with COPD: Protocol of the MORDYC study.

Dyspnea is one of the most reported symptoms of patients with advanced Chronic Obstructive Pulmonary Disease (COPD) and is often undertreated. Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and respiratory adverse effects remain. This study primarily evaluates the impact of oral sustained release morphine (morphine SR) on health-related quality of life and respiratory adverse effects in patients with COPD. Secondary objectives include the impact on exercise capacity, the relationship between description and severity of dyspnea and the presence of a clinically relevant response to morphine, and cost-effectiveness. A single-center, randomized, double blind, placebo controlled intervention study will be performed in 124 patients with COPD who recently completed a comprehensive pulmonary rehabilitation program. Participants will receive 20-30 mg/24h morphine SR or placebo for four weeks. After the intervention, participants will be followed for twelve weeks. Outcomes include: the COPD Assessment Test, six minute walking test, Multidimensional Dyspnea Scale and a cost diary. Furthermore, lung function and arterial blood gasses will be measured. These measures will be assessed during a baseline and outcome assessment, two home visits, two phone calls, and three follow-up assessments. The intervention and control group will be compared using uni- and multivariate regression analysis and logistic regression analysis. Finally, an economic evaluation will be performed from a societal and healthcare perspective. The current manuscript describes the rationale and methods of this study and provides an outline of the possible strengths, weaknesses and clinical consequences.

Comparison of three different techniques for the isolation of viral RNA in sputum.

BACKGROUND: Respiratory infections are a major cause of morbidity and mortality worldwide. A high percentage of all respiratory tract infections are caused by RNA viruses. Real-time PCR is a highly sensitive method for the detection of respiratory viruses in clinical samples. A good RNA isolation protocol is of high importance, since RNA is more unstable than DNA and many clinical samples contain RNAses. OBJECTIVES: To evaluate the performance of three different RNA extraction protocols for the extraction of respiratory viral RNA from sputum samples obtained from patients with the suspicion of a viral respiratory tract infection. STUDY DESIGN: A total of 50 sputum samples, PCR positive for a respiratory RNA virus, were used for viral RNA isolation with the phenol/chloroform method, RTP(®) DNA/RNA virus mini kit and the automated MagNa Pure LC (MPLC) extraction system. After isolation, real-time PCR was performed for the detection of viral RNA in the sputum samples. RESULTS: The MPLC extraction increased the detection probability from 82% (phenol/chloroform) and 86% (RTP(®) DNA/RNA virus mini kit) to 94%. In 16% the RTP(®) DNA/RNA virus mini kit resulted in lower Ct values compared to the phenol/chloroform method, while in 32% the phenol/chloroform resulted in lower Ct values. CONCLUSIONS: The extraction of viral RNA performed with the MPLC extraction method was superior to the extraction with the RTP(®) DNA/RNA virus mini kit and to the extraction with phenol/chloroform. In general, there was no difference in the detection of viral RNA between the phenol/chloroform extraction method and the RTP(®) DNA/RNA virus mini kit.

Identification of microorganisms based on headspace analysis of volatile organic compounds by gas chromatography-mass spectrometry.

The identification of specific volatile organic compounds (VOCs) produced by microorganisms may assist in developing a fast and accurate methodology for the determination of pulmonary bacterial infections in exhaled air. As a first step, pulmonary bacteria were cultured and their headspace analyzed for the total amount of excreted VOCs to select those compounds which are exclusively associated with specific microorganisms. Development of a rapid, noninvasive methodology for identification of bacterial species may improve diagnostics and antibiotic therapy, ultimately leading to controlling the antibiotic resistance problem. Two hundred bacterial headspace samples from four different microorganisms (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumoniae) were analyzed by gas chromatography-mass spectrometry to detect a wide array of VOCs. Statistical analysis of these volatiles enabled the characterization of specific VOC profiles indicative for each microorganism. Differences in VOC abundance between the bacterial types were determined using ANalysis of VAriance-principal component analysis (ANOVA-PCA). These differences were visualized with PCA. Cross validation was applied to validate the results. We identified a large number of different compounds in the various headspaces, thus demonstrating a highly significant difference in VOC occurrence of bacterial cultures compared to the medium and between the cultures themselves. Additionally, a separation between a methicillin-resistant and a methicillin-sensitive isolate of S. aureus could be made due to significant differences between compounds. ANOVA-PCA analysis showed that 25 VOCs were differently profiled across the various microorganisms, whereas a PCA score plot enabled the visualization of these clear differences between the bacterial types. We demonstrated that identification of the studied microorganisms, including an antibiotic susceptible and resistant S. aureus substrain, is possible based on a selected number of compounds measured in the headspace of these cultures. These in vitro results may translate into a breath analysis approach that has the potential to be used as a diagnostic tool in medical microbiology.

Quality of dietary intake in relation to body composition in patients with chronic obstructive pulmonary disease eligible for pulmonary rehabilitation.

BACKGROUND/OBJECTIVES: A poor dietary quality may accelerate disturbances in body composition in chronic obstructive pulmonary disease (COPD), but only limited studies have investigated dietary intake from this perspective. The objective of the current study was to investigate dietary intake in relation to low fat-free mass and abdominal obesity in COPD. SUBJECTS/METHODS: Dietary intake was assessed by means of a cross-check dietary history method in 564 COPD patients referred for pulmonary rehabilitation. The Dutch Food Composition Database was used to calculate nutrient intake, which was compared with the 2006 recommendations from the Dutch Health Council. Body composition was assessed by DEXA scan. RESULTS: In general, the reported intake of macronutrients represented a typical western diet. With regard to micronutrients, vitamin D and calcium intakes were below the recommended levels in the majority of patients (>75%), whereas vitamin A, C and E intakes were below the recommended levels in over one-third of patients. Patients with inadequate vitamin D intake more frequently reported a low intake of protein (P=0.02) and micronutrients (P<0.001). Patients with a low fat-free mass index (FFMI) more often had low intake of protein, while abdominally obese patients more often had low intake of protein and most micronutrients (P<0.05). Patients with both low FFMI and abdominal obesity appeared most often to be consuming a poor-quality diet. CONCLUSIONS: Our data indicate that dietary quality is low in COPD patients referred for pulmonary rehabilitation and differs between patients with different body composition profiles.

[Cognitive impairment in patients with COPD: a review]. / Cognitieve beperkingen bij patiënten met COPD: een overzicht.

COPD (Chronic Obstructive Pulmonary Disease) is a respiratory disease characterized by progressive and largely irreversible airway limitation and extrapulmonary problems. The prevalence of COPD increases with age. Mental health problems, including cognitive capacity limitations, occur frequently. Patients with COPD may have problems with cognitive functioning, either globally or in single cognitive domains, such as information processing, attention and concentration, memory, executive functioning and self-regulation. Possible causes are hypoxemia, hypercapnia, exacerbations and decreased physical activity. Cognitive problems in these patients may be related to structural brain abnormalities, such as gray matter pathologic changes and the loss of white matter integrity. Because of the negative impact on health and daily life, it is important to assess cognitive functioning in patients with COPD in order to optimize patient-oriented treatment and to reduce personal discomfort, hospital admissions and mortality.

The Association Between Dietary Intake and Phenotypical Characteristics of COPD in the ECLIPSE Cohort.

Background: Diet is a potentially modifiable risk factor in the development and progression of many diseases, and there is evidence that diet plays a role in COPD. Objective: Evaluate the relationship between dietary intake and clinical characteristics of COPD in a large and well-characterized population of COPD patients and controls who were part of the ECLIPSE study. Methods: Limited diet records were available from 2,167 participants at 8 time points over a 3-year period. Participants reported the amount they had consumed over the last 24 hours for 8 food categories. Intake of each food group was handled as a dichotomous variable (Yes/last 24 hours at any of the 8 follow-up points vs. No at all 8 points). These 2 groups were then compared using clinical outcome measures at the last available follow-up that included lung function, emphysema, 6-minute walk, St. George's Respiratory Questionaire (SGRQ) scores, the change in these scores over a 3-year period, and inflammatory biomarkers. Multivariate models for each food group and each outcome measure were run to adjust for confounding factors of age, sex, body mass index (BMI), and smoking. Results: Participants who demonstrated recent consumption of foods associated with a healthful diet, including fish, fruit, tea, and dairy products, had greater lung function measures and less decline over time, less emphysema and emphysema progression, greater 6-minute walk and SGRQ scores, and lower levels of certain inflammatory markers. Increasing the number of diet record time points that were included in the analysis improved ability to detect significant associations. Conclusion: Diet as a possible modifiable risk factor in COPD continues to warrant investigation.