Respiratory Medicine

Body composition in COPD; stepping back or moving forward?

A.M.W.J. Schols — 2009-10-12

The past two decades epidemiological and clinical intervention studies have consistently shown that muscle wasting is an important therapeutic target to compress COPD morbidity. Various body composition methods are available to estimate the size of whole body muscle mass. Like other COPD assessment tools, expensive, invasive laboratory tests are generally more accurate than field tests. Evaluation of body composition methods is hampered by absence of a true gold standard except for “carcass analysis”. New methods are therefore compared with reference methods that have proven to be highly accurate and precise for assessment of specific body compartments such as fat mass (hydrostatic weighing), total body water (deuterium dilution) and lean body mass (total body potassium by whole body gamma counting). In this journal Rutten et al. present a critical view on diagnosing muscle wasting by bioelectrical impedance analysis (BIA) and appear to suggest that it is too early to implement body composition in clinical practice due to absence of appropriate reference values for fat-free mass (FFM). Is it indeed time to step back or should we move forward and even accelerate?

Exploring the care needs of patients with advanced COPD: An overview of the literature

2009-10-09

Summary: Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition worldwide and is associated with significant mortality. This paper gives an overview of the relevant literature regarding care needs in advanced COPD from the perspective of the patient or carer, and aims to explore the appropriateness of a palliative care approach in this group. Publications revealed that patients with COPD have a high symptom burden that impacts on quality of life and social functioning. Information provision in COPD is often lacking and the implications of diagnosis and prognosis are not routinely discussed. The impact on families and carers is considerable, many patients have significant care requirements which can affect family relationships. Although patients with COPD have regular contact with health services, access to specialist services and palliative care is poor. This paper highlights the need for increased provision for palliative care in COPD, alongside dedicated education and training for health professionals, and continued research to identify the most appropriate ways of delivering this care.

A daily SMS reminder increases adherence to asthma treatment: A three-month follow-up study

Ulla Strandbygaard, Simon Francis Thomsen, Vibeke Backer — 2009-10-26

Summary: Background: Poor adherence to asthma treatment is a well-recognised challenge and is associated with increased morbidity, mortality and consumption of health care resources. This study examined the impact of receiving a daily text message reminder on one's cell phone on adherence to asthma treatment.Methods: A total of 26 subjects aged 18–45 years, with a clinical history of asthma and a positive methacholine challenge test (PD20≤4μmol) were randomised to receive, or to not receive, a daily short message service (SMS) reminder on their cell phone to take their anti-asthmatic medication. Inhaled corticosteroids to last for eight weeks and a prescription for four additional weeks were given to the subjects. The primary outcome was adherence to asthma treatment. Secondary outcomes were reimbursement of asthma medication, and change in exhaled nitric oxide levels, lung function, and airway responsiveness.Results: The absolute difference in mean adherence rate between the two groups after 12 weeks was 17.8%, 95% CI (3.2–32.3%), p=0.019. No significant differences were observed between the two randomisation groups for the secondary outcomes.Conclusion: Daily text message reminders are already after a short period of observation associated with increased adherence to anti-asthmatic medication.

Asthmatics and ex-smokers respond early, heavy smokers respond late to mailed surveys in Italy

2009-10-26

Summary: Rationale and objectives: Response to mailed epidemiological surveys has decreased in recent decades. Since subjects with respiratory symptoms are usually early responders to surveys performed in Southern Europe, this trend could bias prevalence estimates. The present study aimed at evaluating the impact of non-response bias on prevalence estimates of respiratory symptoms and smoking habits.Methods: In 9 centres, participating in the Italian Study on Asthma in Young Adults (ISAYA), random samples of people aged 20–45 years were administered a mailed questionnaire between 1998 and 2000. Non-responders were contacted again first by mail and then by phone. Cumulative response percentage was 30.5%, 52.4% and 72.7% (18,873/25,969), respectively, after the 1st, 2nd and 3rd contact.Results: The prevalence of self-reported current asthma, asthma-like symptoms, and chronic cough/phlegm was more than halved from the first contact (5.6%, 17.8%, 14.6% respectively) to the third contact (2.7%, 6.4%, 6.9%). This pattern was less pronounced when considering allergic rhinitis and past asthma, whose prevalence decreased, respectively, from 21.5% to 15.6% and from 3.5% to 2.6%. At the same time the proportion of current smokers increased from 29.2% to 38%, while the proportion of ex-smokers decreased from 16.5% to 10.1%. In a multinomial logistic model current asthma, asthma-like symptoms, chronic cough/phlegm and smoking habits, and to a lower extent past asthma and allergic rhinitis, were significant predictors of late response.Conclusions: In Italy when response percentage is low, the prevalence of current asthma, chronic cough/phlegm and ex-smokers is overestimated, while the proportion of current smokers is underestimated.

Adolescents with asthma: Consequences of transition from paediatric to adult healthcare

Sten-Erik Bergström, Kerstin Sundell, Gunilla Hedlin — 2009-11-04

Summary: Purpose: A prospective follow-up of adolescents with asthma designed to identify risk factors for deterioration during and after transfer from paediatric to adult healthcare.Methods: Adolescents (n=150) with asthma being transferred from paediatric to adult healthcare were recruited consecutively and those with mild/moderate asthma assigned randomly to primary care or specialized care at an adult asthma clinic. Tests of pulmonary function, bronchial responsiveness and working capacity and skin prick tests were performed at the time of entry into the study and two and/or five years later.Results: Initially, 88.7% of the subjects demonstrated at least one positive skin prick test. During the five-year follow-up, FEV1 improved, while FEV1/FVC remained unchanged. Bronchial hyperresponsiveness was present in 71% of the subjects at the time of inclusion and 59% five years later, while 20 developed hyperresponsiveness during this period. Poor adherence to treatment, female gender and inhalation of steroids exerted negative impacts on logPD20. The risk for persistence of bronchial hyperresponsiveness was elevated by poor adherence and attenuated by regular exercise. The decline observed in working capacity demonstrated no correlation to the risk factors examined. Subjects with mild/moderate asthma who received primary or specialized care exhibited similar pulmonary function, responses to a histamine challenge and working capacities.Conclusions: During a five-year follow-up of asthmatic adolescents leaving paediatric care, pulmonary function rarely deteriorated, but bronchial hyperresponsiveness persisted. Female gender and poor adherence to treatment exerted negative impact on bronchial hyperresponsiveness. Mild/moderate asthma was managed equally effectively with primary or specialized care.

Effect of omalizumab on peripheral blood eosinophilia in allergic asthma

M. Massanari, S.T. Holgate, W.W. Busse, P. Jimenez, F. Kianifard, R. Zeldin — 2009-10-21

Summary: Eosinophilia is an established marker of asthma-related inflammation. We assessed the effect of omalizumab on peripheral blood eosinophil counts using a pooled analysis of data from five randomized, double-blind, placebo-controlled studies in patients with moderate-to-severe persistent allergic asthma receiving moderate-to-high-dose inhaled corticosteroids (omalizumab, n=1136; placebo, n=1100). Relationships between omalizumab, peripheral blood eosinophils, serum free IgE concentrations and clinical outcomes were explored. Baseline mean eosinophil counts were similar in each treatment group. Post-treatment eosinophil counts were significantly reduced from baseline in the omalizumab group (p<0.0001) but were not significantly different in the placebo group. Greater reductions in eosinophil counts were observed in patients who had post-treatment free IgE levels <50ng/mL. Three studies included steroid-stable and steroid-reduction phases. At the end of each phase in these studies, a significantly greater reduction in eosinophil counts was achieved in the omalizumab group compared with the placebo group (p<0.0001). A consistent pattern of improved clinical outcomes/decreased eosinophils and worsened clinical outcomes/increased eosinophils was observed for both omalizumab and placebo treatment groups. The findings from our analysis of a large patient population are consistent with earlier reports of the inhibitory effect of omalizumab on eosinophils.

Pulmonary function correlates with arterial stiffness in asthmatic patients

Zeev Weiler, Yuri zeldin, Eli Magen, Doron Zamir, Mona I. Kidon — 2009-11-05

Summary: Background: At the population level, asthma has been associated with chronic systemic inflammation as well as adverse cardiovascular outcomes.Objectives: The aim of this study was to investigate peripheral vascular hemodynamic variables of arterial stiffness (AS) and their relationship to pulmonary function tests in asthmatic patients.Methods: Young asthmatic patients from the tertiary center for pulmonary diseases at the Barzilai Medical Center underwent pulmonary function evaluation and non-invasive radial artery hemodynamic profiling, pre- and post-exercise. Results were compared to age matched, non-asthmatic controls.Results: 23 young asthmatics and 41 controls, completed all evaluation points. Pulmonary flow parameters were significantly reduced in the asthma group at all points. There were no differences between groups in BMI, blood pressure, pulse rate or measurements of AS at baseline or after bronchodilation. The % predicted forced expiratory volume in the first second at baseline (FEV1%) in asthmatics was positively correlated with the small arteries elasticity index (SAEI) and negatively correlated with the systemic vascular resistance (SVR) in these patients. These correlations were not observed in non-asthmatic controls. In multifactorial regression FEV1 remained the major factor associated with measurements of AS in asthmatic patients, while gender was the only significant factor in non-asthmatic controls.Conclusions: Significant correlations between measurements of AS and FEV1 in young asthmatics, suggest the presence of a common systemic, most likely inflammatory pathway involving both the cardiovascular and respiratory systems.

Clinical significance of decline in serum IgE levels in allergic bronchopulmonary aspergillosis

2009-10-05

Summary: Background and Aims: The total serum IgE level is a marker of immunological activity in allergic bronchopulmonary aspergillosis (ABPA), and a 35% decline beyond six weeks is traditionally taken as criteria for remission. The aim of this study was to evaluate the magnitude and clinical significance of decline in serum IgE levels at six weeks in patients with ABPA.Methods: All consecutive patients with ABPA presenting to the Chest Clinic were followed up with clinical evaluation, total IgE levels and chest x-ray every six weeks for three months. We analyzed the percentage decline in IgE levels and correlated it with clinical outcomes of relapse and complete remission.Results: Of the 242 asthmatics, 54 were diagnosed with ABPA (29 males, 25 females; mean age-34 years). There was clinical and radiological improvement at six weeks in all patients receiving glucocorticoid therapy. The IgE levels fell by a mean of 38.8%, and the decline was significantly higher in patients with baseline IgE levels >2500IU/mL than with levels ≤2500IU/mL (44% vs. 26%). Twenty-two patients did not attain a 35% decline in IgE levels, and this number was significantly higher in patients with IgE levels <2500IU/mL. On multivariate analysis, the decline in IgE levels at six weeks did not predict clinical outcomes.Conclusions: A 35% decline in serum IgE levels at six weeks is not seen in all patients with ABPA, and the decline is slower in patients with baseline IgE levels <2500IU/mL. The quantum decline in serum IgE levels does not predict clinical outcomes.

Effects of corticosteroid use on readmission in obstructive lung disease

2009-09-25

Summary: Objective: Obstructive lung disease is a leading cause of morbidity and mortality worldwide. Some patients are readmitted, but currently predicting parameters for identifying these patients are lacking. The aim of this study was to quantify the incidence of readmission in chronic obstructive lung disease and to identify determinants for hospital readmission.Methods: We conducted a cohort study using the PHARMO record linkage system, including demographic details and complete medication histories of more than two million community-dwelling residents in the Netherlands from 1985 onwards. Eligible patients were adult users of inhaled corticosteroids (ICS) with an admission for obstructive lung disease. The outcome parameter was readmission within a follow-up period of one year.Results: We identified 605 ICS users with an admission for chronic obstructive lung disease, 132 of these patients were readmitted. Readmission was associated with a high Chronic Disease Score (adjusted HR 2.4; 95% CI 1.1–5.3). Patients using short courses of systemic corticosteroids only (adjusted HR 0.5; 95% CI 0.4–0.8) or combined with antibiotics (adjusted HR 0.4; 95% CI 0.2–0.6) were at decreased risk of readmission. The effect of high-dose ICS use varied over time.Conclusions: Treatment of exacerbations out of the hospital was associated with a decreased risk of readmission, while patients with multiple chronic diseases are at increased risk of readmission for obstructive lung disease. These patients should be educated and should be invited to consultation more often to be able to detect exacerbation in an early phase and start treatment as early as possible.

Bilevel ventilation during exercise in acute on chronic respiratory failure: A preliminary study

Collette Menadue, J.A. Alison, A.J. Piper, D. Flunt, E.R. Ellis — 2009-10-05

Summary: To determine the immediate effects of bilevel non-invasive ventilation plus oxygen (NIV+O2) during exercise compared to exercise with O2 alone in people recovering from acute on chronic hypercapnic respiratory failure (HRF), a randomised crossover study with repeated measures was performed.Eighteen participants performed six minute walk tests (6MWT) and 16 participants performed unsupported arm exercise (UAE) tests with NIV+O2 and with O2 alone in random order.Distance walked increased by a mean of 43.4m (95% CI 14.1 to 72.8, p=0.006) with NIV+O2 compared to exercise with O2 alone. In addition, isotime oxygen saturation increased by a mean of 5% (95% CI 2–7, p=0.001) and isotime dyspnoea was reduced [median 2 (interquartile range (IQR) 1–4) versus 4 (3–5), p=0.028] with NIV+O2. A statistically significant increase was also observed in UAE endurance time with NIV+O2 [median 201s (IQR 93–414) versus 157 (90–342), p=0.033], and isotime perceived exertion (arm muscle fatigue) was reduced by a mean of 1.0 on the Borg scale (95% CI −1.9 to −0.1, p=0.037) compared with O2 alone.Non-invasive ventilation plus O2 during walking resulted in an immediate improvement in distance walked and oxygen saturation, and a reduction in dyspnoea compared to exercise with O2 alone in people recovering from acute on chronic HRF. The reduction of dyspnoea during walking and arm muscle fatigue during UAE observed with NIV+O2 may allow patients to better tolerate exercise early in the recovery period.

Tiotropium 5μg via Respimat and 18μg via HandiHaler; efficacy and safety in Japanese COPD patients

M. Ichinose, T. Fujimoto, Y. Fukuchi — 2009-12-07

Summary: Background and objectives: To compare the efficacy and safety of tiotropium inhaled via Respimat® Soft Mist Inhaler, a multidose propellant-free inhaler and HandiHaler®, a single-dose dry powder inhaler, in a phase 2 study of Japanese COPD patients.Methods: Patients with FEV1≤70% predicted, FEV1/FVC≤70% and a smoking history of >10 pack-years received tiotropium once daily via Respimat® (5μg) and HandiHaler® (18μg) for 4 weeks each in a randomised, double-blind, double-dummy, two-way crossover study. Lung function, adverse events, pharmacokinetics and safety were assessed.Results: Of 184 patients screened, 134 were evaluable. The trough FEV1 response on Day 29 showed Respimat® to be non-inferior to HandiHaler® (mean treatment difference, 0.008L; 95% CI, −0.009 to +0.024L; p<0.001). Peak and average FEV1 and FVC responses on Day 1 and Day 29 were very similar for the two treatments. Tiotropium plasma levels and excretion kinetics showed a similar profile of systemic exposure for the two formulations of tiotropium. Adverse events were reported by similar numbers of patients on each treatment, i.e. 27.9 and 30.6% in the Respimat® and HandiHaler® groups, respectively.Conclusions: In Japanese patients with COPD, tiotropium Respimat® 5μg and tiotropium HandiHaler® 18μg showed a similar profile of efficacy, safety and pharmacokinetics.

Muscle training with repetitive magnetic stimulation of the quadriceps in severe COPD patients

2009-11-06

Summary: Background: Previous studies have used electrical neuromuscular stimulation as a physical training method in patients with severe COPD. We introduce the use of the more tolerable magnetic stimulation for the same purpose, investigating the effectiveness of an eight-week protocol.Methods: Eighteen patients with severe COPD were randomly assigned to a magnetic stimulation training protocol, n=10, FEV1=30% (SD: 7) or to parallel clinical monitoring, control group, n=8, FEV1=35% (SD: 8). During eight weeks, patients were stimulated for 15min on each quadriceps femoris, three times per week. Quadriceps muscle strength and endurance measurements, quality-of-life questionnaires (SF36, SGRQ) and a six-minute walking test were all carried out before and after the training period in the stimulated and control subjects.Results: All patients completed the training with increasing intensity of stimulation, displaying a significant improvement in voluntary quadriceps strength (17.5% of the baseline value) and exercise capacity, with a mean increase of 23m in the six-minute walking test. The questionnaire scores showed greater increases in quality-of-life scores in the trained subjects compared to the controls, particularly in the physical function areas: mean increments in SF36 in “physical function”: +26, “role limitations due to physical problems”: +40 and “vitality”: +17.5, while +13, −4 and +1, respectively in controls. Saint George's “Activity” score improved by 19.6 points, for 11.5 in controls.Conclusions: In COPD patients who are limited due to dyspnoea, magnetic neuromuscular stimulation of the quadriceps constitutes a feasible training method for the lower limbs, with positive effects on the muscle function, effort capacity and perception areas.

Inhaled corticosteroids and risk of pneumonia in newly diagnosed COPD

Min J. Joo, David H. Au, Marian L. Fitzgibbon, Todd A. Lee — 2009-11-02

Summary: Introduction: The use of inhaled corticosteroids (ICS) in COPD may be associated with an increased risk of pneumonia. Little is known of this risk in newly diagnosed COPD patients. The objective of this study was to determine if the use of ICS among newly diagnosed COPD patients is associated with an increased risk of pneumonia hospitalizations.Methods: Using data from the Department of Veterans Affairs and Centers for Medicare and Medicaid Services, a nested case–control study was performed. We identified patients 65 years of age or older with a new diagnosis of COPD from 1998 to 2002. A total of 145,586 patients were identified. Cases were defined based on hospitalization for pneumonia and exposure was prior use of ICS. Up to 10 controls were matched for each case based on age, sex, month and year of the case. The association between ICS use and pneumonia was evaluated with conditional logistic regression controlling for age, comorbidities, medication classes associated with the risk of pneumonia, and markers of COPD severity.Results: There were 13,995 cases of pneumonia. The cohort was predominantly male with an average age of 75.1 (SD=5.4) years. The rate of pneumonia was 6.4 per 100 person-years. After adjustment for covariates, patients with current use of ICS were 1.38 (95% CI, 1.31–1.45) times more likely to have a hospitalization for pneumonia than those without current use of ICS.Conclusions: The use of ICS among patients with newly diagnosed COPD is associated with an increased risk of hospitalization for pneumonia.

Comorbidity and gender-related differences in patients hospitalized for COPD. The ECCO study

2009-11-02

Summary: Rationale: Patients hospitalized for a COPD exacerbation are usually of advanced age, with functional deterioration, and suffering an increased number of associated conditions, but little is known about gender differences. Our hypothesis is that the frequency and type of comorbidities differ in male and female COPD patients.Material and methods: A cross-sectional, multicentre study of patients hospitalized for a COPD exacerbation. All of them had COPD confirmed by baseline forced spirometry with a bronchodilator test. Comorbidity information was collected using the Charlson index, and an ad hoc questionnaire that included other common conditions not included in the Charlson index.Results: We studied 398 patients, 353 men (89%) and 45 women (11%), with a mean (S.D.) age of 73.7 (8.9) years and a percent predicted FEV1 of 43.2 (12.5). The mean score of the Charlson index was 2.7 (2.0), with no differences by gender; in contrast, the mean number of all comorbid conditions assessed was 3.7 (1.7) in men and 1.8 (1.8) in women (p < 0.05). Overall, 55% of the patients had arterial hypertension, 26% diabetes mellitus, 27% chronic heart failure, and 17% ischemic heart disease. Female COPD patients had a lower prevalence of ischemic heart disease (p = 0.008) and alcoholism (p = 0.03), but presented more frequently with chronic heart failure (p = 0.03), osteoporosis (p = 0.007) and diabetes mellitus without complications (p = 0.02).Conclusions: Comorbidities are common in patients hospitalized for a COPD exacerbation, but their relative distribution varies by gender. The exclusive use of the Charlson index underestimates comorbidities in COPD patients.

Prevalence and predictors of vertebral fracture in patients with chronic obstructive pulmonary disease

Sumit R. Majumdar, Cristina Villa-Roel, Kristin J. Lyons, Brian H. Rowe — 2009-10-15

Summary: Objectives: Patients with COPD are at risk for osteoporosis-related vertebral compression fractures (VCF) which predispose to more fractures and worsening pulmonary function. Our objectives were to: 1 document VCF prevalence in COPD patients; and 2 determine the independent correlates of VCF.Methods: From 2004–2006, we prospectively recruited consecutive consenting COPD patients presenting with acute exacerbation at three Canadian Emergency Departments (ED). We collected clinical and pulmonary function data. Primary outcome was radiologist documented VCF on chest radiograph. Multivariable logistic regression was used for all adjusted analyses.Results: Overall, 245 patients were studied; 37% were ≥75 years and 44% were women. Prevalence of VCF documented by chest radiograph was 22 of 245 (9%; 95%CI 6–13%). Almost half (10 of 22 [43%]) of VCF patients were not treated for osteoporosis and all 10 received oral steroids. Compared to patients without fractures, those with VCF were older (p=0.014), had COPD of longer duration (p=0.09) and greater severity (mean FEV1 0.9 vs 1.1L; p=0.05), and had lower body mass index [BMI] (median 26 vs 28; p=0.01). Across BMI quartiles (from heaviest [median 37] to lightest [median 21]) the prevalence of VCF progressively increased (2%, 8%, 10%, 21%; p<0.001). In analyses adjusted for age, sex, and COPD duration, the only independent correlate of VCF was BMI: VCF increased as BMI decreased from heaviest (OR=1) to lightest (OR=11.0) quartiles (p=0.025).Conclusions: Almost one-tenth of COPD patients presenting with acute exacerbation have chest radiographs documenting VCF. About half of patients with VCF were not treated for osteoporosis, but all were started on oral steroids. Our findings suggest chest radiograph reports may represent an important case-finding tool for VCF, particularly in underweight patients with COPD.

Additive effects of transdermal tulobuterol to inhaled tiotropium in patients with COPD

2009-10-30

Summary: Background: The current mainstream treatment for COPD is bronchodilators alone or in combination. The effects of a β2-agonist, tulobuterol, administered transdermally, have been reported to last for 24h. However, there are no reports on the efficacy of tulobuterol combined with an anticholinergic. In this study, we investigated the efficacy and safety of transdermal tulobuterol combined with inhaled tiotropium in COPD.Methods: After a 2-week run-in period, 103 stable COPD patients aged ≥40 years were randomized into two groups: inhaled tiotropium (18μg, Tio group) or transdermal tulobuterol (2mg) combined with inhaled tiotropium (18μg, Tio+Tulo group) for 8 weeks. Primary endpoints were pulmonary function and severity of dyspnea. The St. George's Respiratory Questionaire (SGRQ) score was a secondary endpoint.Results: In both groups, FEV1 and FVC as well as dyspnea improved significantly after 8 weeks. In a comparison of both groups, percentage changes in IC and morning and evening peak expiratory flow were significantly greater in the Tio+Tulo group than in the Tio group. In addition, significant improvement in SGRQ score was observed in the Tio+Tulo group only. The risk of adverse events related to the study drugs was not increased.Conclusion: In COPD patients, additional administration of transdermal tulobuterol to inhaled tiotropium produced significant benefits in dyspnea and SGRQ score as well as pulmonary function. These benefits may be due to a reduction in pulmonary hyperinflation resulting from improvement of peripheral airflow obstruction through tulobuterol via the systemic circulation.

Systemic and airway inflammation and the presence of emphysema in patients with COPD

2009-10-26

Summary: The aim of this study was to determine the impact of HRCT-confirmed emphysema on biomarkers evaluating airway and systemic inflammation in COPD patients.Forty-nine consecutive male COPD outpatients with stable COPD were divided in two groups according to the presence or absence of emphysema on HRCT. Patients underwent pulmonary function tests, plus assessment of exercise capacity, body composition and quality of life. Biomarkers were measured in serum (CRP, interleukin-6, TNF-α, leptin, adiponectin, osteocalcin, insulin growth factor-1, and systemic oxidative stress), in plasma (fibrinogen and VEGF) and in whole blood (B-type natriuretic peptide). TNF-α, 8-isoprostane and pH were additionally measured in exhaled breath condensate.Patients with emphysema had more severe lung function impairment, lower body-mass index and fat-free mass index, and poorer quality of life. Additionally, they presented increased systemic oxidative stress and plasma fibrinogen and lower BNP compared to patients without emphysema. After proper adjustment for disease severity, all differences remained with the exceptions of body-mass index, fat-free mass index and BNP.COPD patients with HRCT-confirmed emphysema present increased systemic oxidative stress and fibrinogen, suggesting that they may be more prone to the systemic consequences of COPD compared to patients without emphysema.

Systemic mannose-binding lectin is not associated with chronic obstructive pulmonary disease

2009-10-16

Summary: Mannose-binding lectin (MBL) deficiency is associated with increased susceptibility to airways infections and autoimmunity. We examined whether MBL deficiency was more common in COPD patients, and whether MBL deficiency was associated with COPD severity.415 COPD patients and 231 healthy subjects, aged 40–75, were examined in 2006/07. Plasma MBL levels were determined by ELISA. Low or deficient MBL levels were defined as plasma levels below 500ng/mL or 100ng/mL respectively. Logistic regression models determined factors associated with MBL deficiency; with explanatory variables study category, sex, age, smoking, comorbid heart disease, and CRP. For COPD severity, explanatory variables were FEV1, exacerbation history, hypoxia, respiratory symptoms, inhaled steroids, and CRP.18.2% of healthy subjects and 22.2% of patients had MBL levels below 100ng/mL (p=0.23); 42.9% of healthy subjects and 49.6% of patients had levels below 500ng/mL (p=0.10). After adjustment for co-variables, patients had an OR (95% CI) of 1.26 (0.7, 2.2) for having MBL levels below 100ng/mL compared with healthy subjects, and an OR (95% CI) of 1.06 (0.7, 1.7) for having levels below 500ng/mL. Among the COPD patients, none of the disease variables were associated with MBL deficiency.No association was found between MBL deficiency and COPD or COPD severity.

Acute effects of NPPV in interstitial lung disease with chronic hypercapnic respiratory failure

Dirk Koschel, Sabin Handzhiev, Bärbel Wiedemann, Gert Höffken — 2009-10-19

Summary: Objective: A case series evaluating the acute effects of noninvasive positive pressure ventilation (NPPV) in patients with chronic hypercapnic respiratory failure (HRF) secondary to interstitial lung diseases (ILD).Patients and methods: Ten patients with ILD were retrospectively evaluated. All had restrictive lung function (mean TLC, 47.6±12.6% predicted) and chronic hypercapnic respiratory failure (mean pH=7.39±0.02). Arterial blood gas analysis and lung function were compared before and after the application of controlled pressure-limited NPPV.Results: Daytime PaCO2 during spontaneous breathing decreased by 5.4±1.3mmHg (95% confidence interval, 4.5–6.3), from 57.7±5.1mmHg to 52.3±5.9 (p<0.001); while daytime PaO2 increased by 3.4±3.3mmHg (95% confidence interval, 1.0–5.8), from 63.7±3.5mmHg to 67.1±3.4 (p=0.01); and TLC increased by 3.9±4.5% (95% confidence interval, 0.7–7.1), from 47.6±12.6%mmHg to 51.5±10.0% (p=0.023).Conclusions: In patients with ILD and chronic HRF controlled NPPV is tolerated and can acutely improve blood gas levels. Further studies examining the long-term benefits need to be explored.

The SF-36 and SGRQ: Validity and first look at minimum important differences in IPF

2009-10-08

Summary: Rationale: Health-related quality of life (HRQL) is an important outcome in drug trials. Little is known about how the Short Form-36 (SF-36) and Saint George's Respiratory Questionnaire (SGRQ) perform in idiopathic pulmonary fibrosis (IPF).Objectives: To examine the validity of the SF-36 and SGRQ and to determine scores from each that would constitute a minimum important difference (MID).Methods: We analyzed data from a recently completed trial that enrolled subjects with well-defined IPF who completed the SF-36, SGRQ, and Baseline/Transition Dyspnea Index at baseline and six months. We compared mean changes in HRQL scores between groups of subjects whose disease severity changed over six months according to clinical anchors (FVC, DLCO, and dyspnea). We estimated the MID for each domain by using both anchor- and distribution-based approaches.Main results: Results supported the validity of the SF-36 and SGRQ for use in longitudinal studies. Mean changes in domain scores differed significantly between subjects whose clinical status improved and those whose clinical status declined according to the anchors. MID estimates for the SF-36 ranged from 2–4 points and from 5–8 points for the SGRQ.Conclusion: In IPF, the SF-36 and SGRQ possess reasonable validity for differentiating subjects whose disease severity changes over time. More studies are needed to continue the validation process, to refine estimates of the MIDs for the SF-36 or SGRQ, and to determine if a disease-specific instrument will perform better than either of these.

Risk factors for idiopathic pulmonary fibrosis in a Mexican population. A case-control study

2009-09-27

Summary: The etiology of idiopathic pulmonary fibrosis (IPF) remains poorly understood, but some studies have suggested that cigarette smoking or other occupational or environmental exposures, diabetes mellitus, or gastroesophageal reflux may play a role. In this study we evaluated the clinical records of a group of 97 consecutive patients with IPF, and 560 patients suffering 5 different respiratory disorders that were examined as controls: asthma (n=111), chronic obstructive pulmonary disease (n=132), squamous cell lung carcinoma (n=118), lung adenocarcinoma (n=101) and patients with otorhinolaryngology problems but without lung disease (n=98). In bivariate analyses male sex, diabetes mellitus and being former cigarette smoker were associated with IPF. After adjusting by these variables, multivariate analysis revealed that type 2 diabetes mellitus [11.3% in IPF patients vs 2.9% in controls, OR=4.3 (95% CI: 1.9–9.8), p<0.0001] was an independent risk factor associated to IPF. Our results provide additional evidence of a putative relationship between DM2 and idiopathic pulmonary fibrosis. Experimental research is necessary for thorough assessment of the pathogenic mechanisms involved in this association.

Infectious pleural effusions can be identified by sTREM-1 levels

2009-10-16

Summary: Background and objective: Conventional methods to establish pleural infection are time-consuming and sometimes inadequate. Biomarkers may aid in making rapid diagnosis of infection. In an observational study we evaluated and compared the diagnostic value of pleural fluid levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), C-reactive protein and procalcitonin in intensive care patients with pleural effusions.Methods: Thirty-six patients with de novo pleural effusions were included and 20 patients with pleural effusions after cardiothoracic surgery and 20 patients with pleural effusions after esophagus surgery acted as controls. Levels of sTREM-1, C-reactive protein and procalcitonin were measured in pleural effusions.Results: Levels of sTREM-1 were highest in empyemas, followed by infectious exudates. Levels of sTREM-1 were low in transudates and non-infectious exudates. C-reactive protein levels were highest in exudates and empyemas, while procalcitonin levels were highest in exudates. Pleural fluid with positive culture results contained higher sTREM-1 and C-reactive protein levels as compared to samples with negative culture results. A cut-off level of 50pg/mlsTREM-1 yielded a sensitivity of 93% and a specificity of 86%, while these were 87% and 67% respectively for a cut-off value of 7.5μg/ml C-reactive protein, and 60% and 64% respectively for a cut-off value of 0.15 ng/ml procalcitonin.Conclusion: sTREM-1 is superior to C-reactive protein and procalcitonin in detecting infection.

Increased oral nitric oxide in obstructive sleep apnoea

2009-10-26

Summary: Background: Hypoxia and snoring-related mechanical trauma contribute to airway inflammation in obstructive sleep apnoea (OSA). Increased exhaled nitric oxide (FENO), an airway inflammation marker, has been reported in OSA patients. We propose the measure of NO in the oral cavity (oNO) as marker of oropharyngeal inflammation in OSA.Methods: We compared oNO and FENO of 39 OSA patients with those of 26 mild asthmatics (ASTHMA), 15 patients with chronic rhinitis or rhinosinusitis (CRS) and 24 healthy subjects. A special device was used for oNO measurement. Apnoea/hypopnoea index (AHI), oxygen desaturation index, mean and nadir SaO2 were calculated from the polysomnography.Results: oNO was significantly increased in OSA (104.2 95%CI 80.2–135.5ppb) as compared to ASTHMA (71.9 95%CI 56.3–91.9ppb; p=0.015), CRS (54.4 95%CI 40.2–73.7ppb; p=0.009) and healthy subjects (63.6 95%CI 59–73ppb; p<0.001). oNO was directly related to AHI (r=0.466, p=0.003) and to minutes slept with SaO2 <90% (r=0.471, p=0.011) and it was inversely related to nadirSaO2 (r=−0.393, p=0.018). FENO was highest in asthmatics (40.3 95%CI 32.5–50.1ppb) and only slightly elevated in OSA (23.1 95%CI 19,8–28.3ppb) and CRS (22.8 95%CI 16.8–32.5ppb).Conclusions: The finding that oral NO is increased in OSA and is related to upper airway obstructive episodes and to hypoxemia severity, strengthens the clinical and pathogenic role of oral inflammation in OSA.

Response to Drs Ramon Fernandez and Gemma Rubinos

Tomomasa Tsuboi, Toru Oga, Kazuo Chin, Kazuko Machida — 2009-11-30

We are grateful for the comments of Drs Ramon Fernandez and Gemma Rubinos regarding our article in Respiratory Medicine dealing with ventilator mode in long-term non-invasive positive pressure ventilation (NPPV).