Mortality of patients with COPD participating in chronic disease management programmes: a happy end?

BACKGROUND: Concerns about increased mortality could question the role of COPD chronic disease management (CDM) programmes. We aimed at extending a recent Cochrane review to assess the effects of CDM on mortality in patients with COPD. METHODS: Mortality data were available for 25 out of 29 trials identified in a COPD integrated care systematic review. Meta-analysis using random-effects models was performed, followed by subgroup analyses according to study length (3-12 months vs >12 months), main intervention component (exercise, self-management, structured follow-up) and use of an action plan. RESULTS: The meta-analysis showed no impact of CDM on mortality (pooled OR: 1.00, 95% CI 0.79 to 1.28). CONCLUSIONS: These results do not suggest that CDM programmes expose patients with COPD to excessive mortality risk.

Agreement between spirometers: a challenge in the follow-up of patients and populations?

BACKGROUND: Long-term cohort studies and lung function laboratories are confronted with the need for replacement of spirometers. Lack of agreement between spirometers might affect the longitudinal comparison of data, notably when replacing conventional by portable spirometers. OBJECTIVES: To compare the handheld EasyOne (EO) with the conventional SensorMedics (SM) spirometer, and to analyze the interdevice reproducibility of EO spirometers. METHODS: In total, 82 volunteers completed spirometry sessions with 1 SM and 2 of 3 EO spirometers following a Latin square design. Analyses of differences in forced vital capacity (FVC), forced expiratory flow in 1 s (FEV1), FEV1/FVC and mean forced expiratory flow calculated between 25 and 75% of the FVC between spirometers used a mixed effect model with a random intercept for each subject and the effect of the device as fixed effect adjusted for sex, age, height and order of spirometer tested. Bland-Altman plots show the 95% limits of agreement. RESULTS: Comparisons between EO and SM showed relatively small mean differences of <3%, but systematically lower values for FVC and FEV1 in all EO devices. The 95% agreement exceeded the limits for FEV1 by 50 ml in 2 EO spirometers. The EO interdevice comparisons showed mean differences and limits of agreement within established thresholds, thus indicating fair accuracy when comparing devices. Repeats with the same spirometer did not result in statistically significant differences. CONCLUSIONS: This study suggests fair agreement between the handheld and the conventional spirometer. Differences slightly exceeding limits for FEV1 in 2 EO devices might be considered mostly irrelevant for clinical practice. However, the systematically lower FVC and FEV1 observed with EO may be significant for epidemiological studies, thus justifying inspection before replacing devices.

[What is the role of outdoor air pollution in asthma?]. / Quel est le rôle de la pollution atmosphérique dans l'asthme?

Strong scientific evidence has shown that ordinary peaks of outdoor air pollution worsen the symptoms and control of asthma. As for chronic exposure, elevated mean level of local, near-road air pollution may cause increased incidence of asthma among children, and probably also among adults. By contrast, while there is no doubt that air pollution worsens allergic inflammatory processes, it is not clearly established that it may increase allergic sensitization among the general population. In this regard, more research is needed, particularly on the effects of outdoor air pollution in the early periods of life.

[Chronic obstructive pulmonary disease: risk and benefit of testosterone therapy]. / Bronchopneumopathie chronique obstructive: risques et bénéfices d'un traitement de testostérone.

Muscular wasting is frequently encountered in COPD patients and is related to a decrease in exercise tolerance, a higher morbidity and mortality. One of the potential causes isa low serum testosterone, which is frequent in COPD. Various studies have explored the effect of testosterone administration alone or as part of combined pulmonary rehabilitation and nutrition protocols. Testosterone had a positive impact on muscle mass and force, and to a lesser extent on physical endurance and respiratory parameters. Future studies should better define appropriate dosage and treatment duration. In the meantime, testosterone should be administered to COPD patients with overt hypogonadism, or in multidisciplinary specialized programmes.

Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies.

Lung transplant recipients present an increased risk for severe complications associated with respiratory infections. We conducted a review of the literature examining the clinical relationship between viral respiratory infection and graft complications. Thirty-four studies describing the clinical impact of influenza, respiratory syncytial virus, parainfluenza, human metapneumovirus, rhinovirus, enterovirus, coronavirus, bocavirus or adenovirus were identified. The detection rate of respiratory viral infection ranged from 1.4% to 60%. Viruses were detected five times more frequently when respiratory symptoms were present [odds ratio (OR) = 4.97; 95% CI = 2.11-11.68]. Based on available observations, we could not observe an association between respiratory viral infection and acute rejection (OR = 1.35; 95% CI = 0.41-4.43). We found a pooled incidence of 18% (9/50) of bronchiolitis obliterans syndrome (BOS) in virus-positive cases compared to 11.6% (37/319) in virus-negative cases; however, limited number of BOS events did not allow to confirm the association. Our review confirms a causal relationship between respiratory viruses and respiratory symptoms, but cannot confirm a link between respiratory viruses and acute lung rejection. This is related in part to the heterogeneity and limitations of available studies. The link with BOS needs also to be reassessed in appropriate prospective studies.

Impact of aerobic exercise capacity and procedure-related factors in lung cancer surgery.

Over the past decades, major progress in patient selection, surgical techniques and anaesthetic management have largely contributed to improved outcome in lung cancer surgery. The purpose of this study was to identify predictors of post-operative cardiopulmonary morbidity in patients with a forced expiratory volume in 1 s <80% predicted, who underwent cardiopulmonary exercise testing (CPET). In this observational study, 210 consecutive patients with lung cancer underwent CPET with completed data over a 9-yr period (2001-2009). Cardiopulmonary complications occurred in 46 (22%) patients, including four (1.9%) deaths. On logistic regression analysis, peak oxygen uptake (peak V'(O2) and anaesthesia duration were independent risk factors of both cardiovascular and pulmonary complications; age and the extent of lung resection were additional predictors of cardiovascular complications, whereas tidal volume during one-lung ventilation was a predictor of pulmonary complications. Compared with patients with peak V'(O2) >17 mL·kg⁻¹·min⁻¹, those with a peak V'(O2) <10 mL·kg⁻¹·min⁻¹ had a four-fold higher incidence of cardiac and pulmonary morbidity. Our data support the use of pre-operative CPET and the application of an intra-operative protective ventilation strategy. Further studies should evaluate whether pre-operative physical training can improve post-operative outcome.

Short-term safety of thoracoscopic talc pleurodesis for recurrent primary spontaneous pneumothorax: a prospective European multicentre study.

The safety of talc pleurodesis is under dispute following reports of talc-induced acute respiratory distress syndrome (ARDS) and death. We investigated the safety of large-particle talc for thoracoscopic pleurodesis to prevent recurrence of primary spontaneous pneumothorax (PSP). 418 patients with recurrent PSP were enrolled between 2002 and 2008 in nine centres in Europe and South Africa. The main exclusion criteria were infection, heart disease and coagulation disorders. Serious adverse events (ARDS, death or other) were recorded up to 30 days after the procedure. Oxygen saturation, supplemental oxygen use and temperature were recorded daily at baseline and after thoracoscopic pleurodesis (2 g graded talc). During the 30-day observation period following talc poudrage, no ARDS (95% CI 0.0-0.9%), intensive care unit admission or death were recorded. Seven patients presented with minor complications (1.7%, 95% CI 0.7-3.4%). After pleurodesis, mean body temperature increased by 0.41°C (95% CI 0.33-0.48°C; p<0.001) at day 1 and returned to baseline value at day 5. Pleural drains were removed after day 4 in 80% of patients. Serious adverse events, including ARDS or death, did not occur in this large, multicentre cohort. Thoracoscopic talc poudrage using larger particle talc to prevent recurrence of PSPS can be considered safe.

Determinants of change in airway reactivity over 11 years in the SAPALDIA population study.

We investigated determinants of change in bronchial reactivity in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA), a population-based cohort with wide age range (29-72 yrs at follow-up). The role of sex, age, atopic status, smoking and body mass index (BMI) on percentage change in bronchial reactivity slope from the baseline value was analysed in 3,005 participants with methacholine tests in 1991 and 2002, and complete covariate data. Slope was defined as percentage decline in forced expiratory volume in 1 s from its maximal value per micromole of methacholine. Bronchial hyperreactivity prevalence fell from 14.3 to 12.5% during follow-up. Baseline age was nonlinearly associated with change in reactivity slope: participants aged <50 yrs experienced a decline and those above an increase during follow-up. Atopy was not associated with change, but accentuated the age pattern (p-value for interaction = 0.038). Smoking significantly increased slope by 21.2%, as did weight gain (2.7% increase per BMI unit). Compared with persistent smokers, those who ceased smoking before baseline or during follow-up experienced a significant decrease in slope (-27.7 and -23.9%, respectively). Differing, but not statistically different, age relationships and effect sizes for smoking and BMI between sexes were found. Mean bronchial reactivity increases after 50 yrs of age, possibly due to airway remodelling or ventilation-perfusion disturbances related to cumulative lifetime exposures.

Effect modification of immunoglobulin E-mediated atopy and rhinitis by glutathione S-transferase genotypes in passive smokers.

BACKGROUND: Experimental studies suggest that glutathione S-transferase (GST) genotypes modify nasal allergen responses induced by secondhand smoke (SHS) exposure. OBJECTIVE: We aimed to investigate whether GSTs affected systemic IgE and allergic rhinitis (AR) in SHS-exposed individuals from a population-based cohort. METHODS: Analyses comprised 2309 never-smokers from the Swiss study on air pollution and health in adults cohort, reporting SHS status at baseline and 11 years later. Outcomes were defined by total serum IgE≥100 kU/L, specific serum IgE determined by Phadiatop® ≥0.35 kU/L and self-reported AR. GSTP1 Ile105Val, GSTM1 and GSTT1 gene deletion genotypes were identified at the follow-up survey. RESULTS: After adjustment for relevant covariates, the homozygous GSTP1 105-Val genotype was negatively associated with high total IgE and high-specific IgE by Phadiatop®, notably in subjects persistently exposed to SHS (OR: 0.20, 95% CI 0.05-0.75; P=0.02, for high total IgE and OR: 0.29, 95% CI 0.10-0.89; P=0.03, for high specific IgE by Phadiatop®). Carrying at least one copy of the GSTM1 gene (non-null) showed a similar association for high specific IgE by Phadiatop® (OR: 0.41, 95% CI 0.22-0.76; P=0.004). No significant associations were found between GSTs and rhinitis. CONCLUSION AND CLINICAL RELEVANCE: In this large cohort, homozygosity for GSTP1 105-Val or carrying the GSTM1 non-null genotype decreased the risk of high total IgE or high specific IgE using Phadiatop® by nearly half in subjects exposed to SHS, as compared with subjects carrying opposite alleles. These findings underline the value of genetic susceptibility when evaluating the effects of environmental exposure on allergic illness. The potential long-term effects of persistent SHS exposure in genetically vulnerable individuals may be of public health relevance.

Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients.

BACKGROUND: Lung transplant recipients are frequently exposed to respiratory viruses and are particularly at risk for severe complications. The aim of this study was to assess the association among the presence of a respiratory virus detected by molecular assays in bronchoalveolar lavage (BAL) fluid, respiratory symptoms, and acute rejection in adult lung transplant recipients. METHODS: Upper (nasopharyngeal swab) and lower (BAL) respiratory tract specimens from 77 lung transplant recipients enrolled in a cohort study and undergoing bronchoscopy with BAL and transbronchial biopsies were screened using 17 different polymerase chain reaction-based assays. RESULTS: BAL fluid and biopsy specimens from 343 bronchoscopic procedures performed in 77 patients were analyzed. We also compared paired nasopharyngeal and BAL fluid specimens collected in a subgroup of 283 cases. The overall viral positivity rate was 29.3% in the upper respiratory tract specimens and 17.2% in the BAL samples (P < .001). We observed a significant association between the presence of respiratory symptoms and positive viral detection in the lower respiratory tract (P = .012). Conversely, acute rejection was not associated with the presence of viral infection (odds ratio, 0.41; 95% confidence interval, 0.20-0.88). The recovery of lung function was significantly slower when acute rejection and viral infection were both present. CONCLUSIONS: A temporal relationship exists between acute respiratory symptoms and positive viral nucleic acid detection in BAL fluid from lung transplant recipients. We provide evidence suggesting that respiratory viruses are not associated with acute graft rejection during the acute phase of infection.

Survival impact of lung transplantation for COPD.

Chronic obstructive pulmonary disease (COPD) is the primary indication for lung transplantation (LTx), but survival benefit is still under debate. We analysed the survival impact of LTx in COPD with a new approach, using the BODE (body mass index, airway obstruction, dyspnoea, exercise capacity) index. We retrospectively reviewed 54 consecutive lung transplants performed for COPD. The pre-transplant BODE score was calculated for each patient and a predicted survival was derived from the survival functions of the original BODE index validation cohort. Predicted and observed post-transplant survival was then compared. In the subgroups with a BODE score >or=7 and <7, a majority of patients (66% and 69%, respectively) lived for longer after LTx than predicted by their individual BODE index. The median survival was significantly improved in the entire cohort and in the subgroup with a BODE score >or=7. 4 yrs after LTx a survival benefit was only apparent in patients with a pre-transplant BODE score of >or=7. In conclusion, while a majority of COPD patients had an individual survival benefit from LTx regardless of their pre-transplant BODE score, a global survival benefit was seen only in patients with more severe disease. This supports the use of the BODE index as a selection criteria for LTx candidates.

Prevalence of airflow obstruction in smokers and never-smokers in Switzerland.

The aim of the present study was to measure age-specific prevalence of airflow obstruction in Switzerland in smokers and never-smokers using pulmonary function tests and respiratory symptoms from 6,126 subjects participating in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults. The lower limit of normal of the forced expiratory volume in 1 s/forced vital capacity ratio was used to define airflow obstruction. Severity of airflow obstruction was graded according to the recommendations of the Global Initiative for Chronic Obstructive Lung Disease. Prevalence of airflow obstruction ranged from 2.5% in subjects aged 30-39 yrs to 8.0% in those aged ≥ 70 yrs. In multivariate analysis, age (OR 2.8, ≥ 70 yrs versus 30-39 yrs), smoking (OR 1.8) and asthma (OR 6.7) were associated with airflow obstruction. Never-smokers constituted 29.3% of subjects with airflow obstruction. Never-smokers with airflow obstruction were younger, more likely to be male and reported asthma more frequently than obstructive smokers. Obstructive smokers and never-smokers had similar level of symptoms and quality of life impairment. The prevalence of airflow obstruction in Switzerland is similar to other developed countries. Never-smokers account for a third of the prevalence, which is higher proportion than elsewhere. Airflow obstruction in never-smokers deserves attention because of its frequency and its similar health impact to that in smokers.

Respiratory viruses in bronchoalveolar lavage: a hospital-based cohort study in adults.

BACKGROUND: The epidemiology of respiratory viruses and their potential clinical impact when recovered in lower respiratory specimens has not been established in the hospital setting. A study was performed to investigate the association between positive viral detection and respiratory infection in an at-risk population. METHODS: 299 adult patients who underwent bronchoalveolar lavage (BAL) procedures were enrolled in a hospital-based prospective cohort study. Descriptive epidemiology is presented of 17 different respiratory viruses detected by reverse transcription-polymerase chain reaction assays in BAL fluid specimens. Multivariate analysis was conducted to identify the clinical characteristics independently associated with the presence of virus. RESULTS: Of 522 BAL fluid specimens analysed, 81% were collected in adult transplant recipients or other immunocompromised patients. Overall, PCR assays identified viral nucleic acid in 91 BAL fluid samples (17.4%). Similar rates of virus-positive BAL fluid were found in the different subpopulations studied (p = 0.113). Coronaviruses were the most frequent (32.3%), followed by rhinovirus (22.6%), parainfluenza (19.5%), influenza (9.7%), respiratory synctial virus (8.6%), human metapneumovirus (4.2%) and bocavirus (3.1%). Multivariate analysis using mixed models showed that respiratory viral infections were associated with a lack of antibiotic treatment response (OR 2.2, 95% CI 1.2 to 4.1) and the absence of radiological infiltrate (OR 0.3, 95% CI 0.2 to 0.8). In lung transplant recipients in whom a respiratory infection was suspected, the respiratory viral detection rate was 24.4% compared with 13.8% overall in other patients (p = 0.02). CONCLUSIONS: In this cohort of hospitalised adults, respiratory viruses detected in BAL fluid specimens were associated with respiratory symptoms, absence of radiological infiltrates and a poor response to antibiotic therapy.

Traffic-related air pollution correlates with adult-onset asthma among never-smokers.

BACKGROUND: Traffic-related pollution is associated with the onset of asthma in children. Its effect on adult-onset asthma is poorly investigated. The SAPALDIA cohort study was used to investigate associations between the 11-year change (1991-2002) in home outdoor traffic-related particulate matter up to 10 microm in diameter (TPM(10)) and the incidence of asthma. METHODS: Never-smokers without asthma at baseline aged 18-60 years in 1991 were eligible for inclusion in the study. Subjects reporting doctor-diagnosed asthma at follow-up were considered incident cases. TPM(10) at baseline and follow-up was predicted and interpolated to subjects' place of residence by dispersion models using emission and meteorological data. Cox proportional hazard models for time to asthma onset were adjusted (age, gender, baseline atopy, body mass index, bronchial reactivity, maternal allergies). RESULTS: Of 2725 never-smokers, 41 reported asthma onset in 2002. Home outdoor TPM(10) concentrations improved during the interval (mean -0.6; range -9 to +7.2; IQR 0.6 microg/m(3)). The incidence of asthma was associated with a change in TPM(10). The hazard ratio (1.30; 95% CI 1.05 to 1.61) per 1 microg/m(3) change in TPM(10) (IQR) was not sensitive to further adjustments (education, workplace exposure, passive smoking, parental asthma or allergies, random area effects, lung function or co-pollutants such as regional, secondary, total PM(10) or proximity to busy roads). CONCLUSION: The data suggest a role for traffic-related pollution in adult-onset asthma. Space, time and source-specific individual assignment of exposure to traffic-related pollution is a key strength of SAPALDIA. It may explain why findings were statistically significant despite the limited number of new cases. As traffic-related pollution prevails, the finding may be of substantial public health relevance.

Titrated sedation with propofol or midazolam for flexible bronchoscopy: a randomised trial.

In this study, we questioned whether propofol provided clinical benefits compared with midazolam in terms of neuropsychometric recovery, safety profile and patient tolerance. Patients, aged >18 yrs, were randomised to receive midazolam or propofol, given by non-anaesthetist physicians to achieve moderate levels of sedation as assessed by the electroencephalographic bispectral index (BIS; between 70 and 85). The primary end-point was the time delay until recovery of the BIS above 90. Other end-points included a neuropsychometric continuous performance test (CPT), serious respiratory adverse events, patient tolerance and physician satisfaction. Neuropsychometric recovery was improved in the propofol compared to the midazolam group as evidenced by faster normalisation of BIS index (5.4+/-4.7 min versus 11.7+/-10.2 min; p = 0.001) and better results at the CPT. In the midazolam group, 15% of patients presented profound sedation precluding CPT completion and one patient required mechanical ventilatory support. Patient tolerance was significantly better in the propofol group, whereas the operator's assessment was comparable in both groups. Compared with midazolam, propofol provided a higher quality of sedation in terms of neuropsychometric recovery and patient tolerance. BIS-guided propofol administration represents a safe sedation technique that can be performed by the non-anaesthesiologist.

Sex-specific effect of body weight gain on systemic inflammation in subjects with COPD: results from the SAPALDIA cohort study 2.

Systemic inflammation may mediate the association between chronic obstructive pulmonary disease (COPD) and extrapulmonary comorbidities. We measured high-sensitivity C-reactive protein (hs-CRP) in COPD and quantified the effect modification by body weight change and sex. Using data from the Swiss study on Air Pollution and Lung Diseases in Adults (SAPALDIA; n = 5,479) with measurements of forced expiratory volume in 1 s (FEV(1)), body weight and hs-CRP, we examined the association of hs-CRP and categories of body weight change (lost weight and weight gained 0-5%, 5-9%, 9-14% and >14%) with fast FEV(1) decline. hs-CRP was elevated both in association with fast FEV(1) decline and body weight gain. Subjects with fast FEV(1) decline and weight gain (>14%) had higher hs-CRP (2.0 mg L(-1) for females versus 1.6 mg L(-1) for males). After adjustment for age, smoking, physical activity, hormonal therapy and diabetes, elevated hs-CRP (>3 mg) was found to be more likely in subjects with fast FEV(1) decline (OR(males) 1.38, OR(females) 1.42) and in those with weight gain >14% (OR(males) 2.04, OR(females) 4.51). The association of weight gain and fast FEV(1) decline predicts a higher level of systemic inflammation. Since the effect of weight gain on systemic inflammation is larger in females than in males, weight gain may be a risk factor for extrapulmonary comorbidities in females with COPD.

Long-term decline in lung function, utilisation of care and quality of life in modified GOLD stage 1 COPD.

BACKGROUND: Little is known about the long-term outcomes of individuals with mild chronic obstructive pulmonary disease (COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). METHODS: A population cohort of 6671 randomly selected adults without asthma was stratified into categories of modified GOLD-defined COPD (prebronchodilator spirometry). Further stratification was based on the presence or absence of respiratory symptoms. After 11 years, associations between baseline categories of COPD and decline in forced expiratory volume in 1 s (FEV(1)), respiratory care utilisation and quality of life as measured by the SF-36 questionnaire were examined after controlling for age, sex, smoking and educational status. RESULTS: At baseline, modified GOLD criteria were met by 610 (9.1%) participants, 519 (85.1%) of whom had stage 1 COPD. At follow-up, individuals with symptomatic stage 1 COPD (n = 224) had a faster decline in FEV(1) (-9 ml/year (95% CI -13 to -5)), increased respiratory care utilisation (OR 1.6 (95% CI 1.0 to 2.6)) and a lower quality of life than asymptomatic subjects with normal lung function (n = 3627, reference group). In contrast, individuals with asymptomatic stage 1 COPD (n = 295) had no significant differences in FEV(1) decline (-3 ml/year (95% CI -7 to +1)), respiratory care utilisation (OR 1.05 (95% CI 0.63 to 1.73)) or quality of life scores compared with the reference group. CONCLUSIONS: In population-based studies, respiratory symptoms are of major importance for predicting long-term clinical outcomes in subjects with COPD with mild obstruction. Population studies based on spirometry only may misestimate the prevalence of clinically relevant COPD.

[Role of antibiotherapy in acute exacerbation of chronic obstructive pulmonary disease]. / Place de l'antibiothérapie dans la prise en charge des exacerbations de BPCO.

Two thirds of the exacerbations of chronic obstructive pulmonary disease (COPD) are caused by infections of the respiratory tract. The causative microorganisms differ according to the degree of COPD severity, previous antibiotic therapy and prior bacterial infections. Antibiotics and intensification of bronchodilator therapy are the cornerstones of the management of moderate and severe exacerbations of COPD. Prompt therapy of COPD exacerbations has been shown to reduce the likelihood of hospitalisation and improve the quality of life. In this article, we have reviewed current recommendations regarding the use of antibiotics in the treatment of COPD exacerbations.

Epidemiology of viral respiratory infections in a tertiary care centre in the era of molecular diagnosis, Geneva, Switzerland, 2011-2012.

Few studies have examined the epidemiology of respiratory viral infections in large tertiary centres over more than one season in the era of molecular diagnosis. Respiratory clinical specimens received between 1 January 2011 and 31 December 2012 were analysed. Respiratory virus testing was performed using a large panel of real-time PCR or RT-PCR. Results were analysed according to sample type (upper versus lower respiratory tract) and age group. In all, 2996 (2469 (82.4%) upper; 527 (17.6%) lower) specimens were analysed. Overall positivity rate was 47.4% and 23.7% for upper and lower respiratory samples, respectively. The highest positivity rate was observed in patients under 18 years old (p <0.001); picornaviruses were the most frequent viruses detected over the year. Influenza virus, respiratory syncytial virus, human metapneumovirus and coronaviruses showed a seasonal peak during the winter season, while picornaviruses and adenoviruses were less frequently detected in these periods. Multiple viral infections were identified in 12% of positive cases and were significantly more frequent in children (p <0.001). In conclusion, we observed significant differences in viral infection rates and virus types among age groups, clinical sample types and seasons. Follow-up of viral detection over several seasons allows a better understanding of respiratory viral epidemiology.