[Bronchoscopic lung volume reduction for COPD: not a real solution after all]. / Endoscopische longvolumereductie voor COPD.

Hyperinflation is an important element in chronic obstructive pulmonary disease (COPD), contributing significantly to dyspnoea and exercise intolerance. Bronchodilators have some, albeit slight, effect on hyperinflation. Lung volume reduction surgery has been advocated in a highly select group of patients with heterogeneous, predominantly upper lobe, emphysema but morbidity and mortality associated with this intervention have hampered its widespread use in respiratory medicine. Bronchoscopic lung volume reduction has recently been introduced. Several studies have shown promising results, again in a highly select group of patients, with clinically relevant effects on symptoms, lung function and quality of life. However, for most COPD patients, prevention and slowing down of disease progression are much more important. Smoking cessation is the single most important intervention to achieve these goals. Furthermore, effective new anti-inflammatory drugs are needed since inhaled steroids, although widely used in COPD, are largely ineffective.

Predictors of 1-year mortality at hospital admission for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are related to high mortality, especially in hospitalized patients. Predictors for severe outcomes are still not sufficiently defined. OBJECTIVES: To assess the mortality rate and identify potential determinants of mortality in a cohort of patients hospitalized for AE-COPD. METHODS: A retrospective, observational cohort study including all consecutive patients admitted between January 1, 2009, and April 1, 2010, for AE-COPD. Potential predictors were assessed at initial presentation at the emergency room. The primary outcome was mortality during 1-year follow-up. Univariate and multivariate time-to-event analyses using Cox proportional hazard models were employed for statistical analysis. RESULTS: A total of 260 patients were enrolled in this study. Mean age was 70.5 ± 10.8 years, 50.0% were male and 63.4% had severe COPD. The in-hospital mortality rate was 5.8% and the 1-year mortality rate was 27.7%. Independent risk factors for mortality were age [hazard ratio (HR) = 1.04; 95% confidence interval (CI) = 1.01-1.07], male sex (HR = 2.00; 95% CI = 1.15-3.48), prior hospitalization for AE-COPD in the last 2 years (HR = 2.56; 95% CI = 1.52-4.30), prior recorded congestive heart failure (HR = 1.75; 95% CI = 1.03-2.97), PaCO2 ≥6.0 kPa (HR = 2.90; 95% CI = 1.65-5.09) and urea ≥8.0 mmol/l (HR = 2.38; 95% CI = 1.42-3.99) at admission. CONCLUSIONS: Age, male sex, prior hospitalization for AE-COPD in the last 2 years, prior recorded congestive heart failure, hypercapnia and elevated levels of urea at hospital admission are independent predictors of mortality within the first year after admission.

Efficacy of confronting smokers with airflow limitation for smoking cessation.

The objective of the present study was to test whether confronting smokers with previously undetected chronic obstructive pulmonary disease (COPD) increases the rate of smoking cessation. In total, 296 smokers with no prior diagnosis of COPD were detected with mild-to-moderate airflow limitation by means of spirometry and randomly allocated to: confrontational counselling by a nurse with nortriptyline for smoking cessation (experimental group); regular counselling by a nurse with nortriptyline (control group 1); or "care as usual" for smoking cessation by the general practitioner (control group 2). Only the experimental group was confronted with their abnormal spirometry (mean forced expiratory volume in one second (FEV(1)) post-bronchodilator 80.5% predicted, mean FEV(1)/forced vital capacity post-bronchodilator 62.5%). There was no difference in cotinine-validated prolonged abstinence rate between the experimental group (11.2%) and control group 1 (11.6%) from week 5-52 (odds ratio (OR) 0.96, 95% confidence interval (CI) 0.43-2.18). The abstinence rate was approximately twice as high in the experimental group compared with control group 2 (5.9%), but this difference was not statistically significant (OR 2.02, 95% CI 0.63-6.46). The present study did not provide evidence that the confrontational approach increases the rate of long-term abstinence from smoking compared with an equally intensive treatment in which smokers were not confronted with spirometry. The high failure rates (> or =88%) highlight the need for treating tobacco addiction as a chronic relapsing disorder.

Smoking cessation treatment by Dutch respiratory nurses: reported practice, attitudes and perceived effectiveness.

OBJECTIVE: To describe Dutch respiratory nurses' current smoking cessation practices, attitudes and beliefs, and to compare these with a survey from the year 2000, before the national introduction of a protocol for the treatment of nicotine and tobacco addiction (the L-MIS protocol). METHODS: Questionnaire survey among all 413 registered respiratory nurses in the Netherlands in 2006. RESULTS: The response rate was 62%. Seventy-seven percent of the respondents reported to have "fairly good" or "good" knowledge of all steps of the L-MIS protocol. Seven out of 10 behavioural techniques for smoking cessation from the protocol were used by more than 94% of the respondents. Seventy-four percent of the respiratory nurses recommended the use of either nicotine replacement therapy (70%) or bupropion (44%). Almost two-thirds (65% of 254) perceived lack of patient's motivation as the most important barrier for smoking cessation treatment; a four-fold increase compared to the year 2000. CONCLUSION: We conclude that respiratory nurses are compliant with the L-MIS protocol. They offer intensive support and use behavioural techniques for smoking cessation more frequently than evidence-based pharmacological aids for smoking cessation. Perceived lack of patient's motivation forms the most important threat to respiratory nurses' future smoking cessation activities. PRACTICE IMPLICATIONS: International guidelines acknowledge that respiratory patients have a more urgent need to stop smoking but have more difficulty doing so. They should be offered the most intensive smoking cessation counselling in combination with pharmacotherapy. This kind of counselling may be more feasible for respiratory nurses than for physicians who often lack time. Their efforts could be increased by reimbursing pharmacological aids for smoking cessation and by developing simple tools to systematically assess motivation to quit and psychiatric co-morbidity in smoking patients.

External validation of a COPD diagnostic questionnaire.

The aim of the present study was to determine the external validity of a recently developed questionnaire for the identification of patients at increased risk of airflow limitation in smokers from the general population in the provinces of Dutch and Belgian Limburg (regions surrounding Maastricht, the Netherlands). As part of a study on the early detection of airflow limitation and subsequent smoking cessation treatment (International Standard Randomised Controlled Trial Number: 64481813), the recently developed chronic obstructive pulmonary disease (COPD) diagnostic questionnaire was used in current smokers aged 40-70 yrs, with a smoking history of >or=10 pack-yrs, who reported one or more respiratory symptom (cough, sputum production or dyspnoea), but who had no diagnosis of a respiratory disease (COPD or asthma). Spirometry performed according to American Thoracic Society/European Respiratory Society criteria served as a reference test. Of the 676 subjects who entered the analyses, 398 showed normal lung function and 278 had a diagnosis of COPD (post-bronchodilator forced expiratory volume in one second/forced vital capacity of <0.70). The ability of the COPD diagnostic questionnaire to discriminate between subjects with and without COPD was poor (area under the receiver operating characteristic curve of 0.65). In a high-risk population consisting of middle-aged current smokers with a smoking history of >or=10 pack-yrs, the chronic obstructive pulmonary disease diagnostic questionnaire is probably not useful as a diagnostic tool for the identification of patients with an increased risk of airflow limitation.

Principles of confrontational counselling in smokers with chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is a major public health problem. The use of spirometry for early detection of COPD is a current issue of debate because of lack of convincing evidence of the additional positive effect of spirometry on smoking cessation. In this article, we present conditions under which early detection of COPD and confrontation may be effective, highlighting the principles of "confrontational counselling". Confronting patients with COPD is not an isolated approach but should be integrated into state-of-the-art smoking cessation treatment. Confrontational counselling should consist of several counselling sessions on an individual, face-to-face level, under supervision of a trained smoking cessation specialist, and in combination with evidence-based pharmacological treatment for smoking cessation.

Association between first-degree familial predisposition of asthma and atopy (total IgE) in newborns.

BACKGROUND: It is generally thought that infants with a first-degree familial predisposition of asthma are at higher risk of developing asthma than infants without predisposition. OBJECTIVE: To investigate whether there is an association between being at high risk for developing asthma and increased level of total IgE in newborns and whether total IgE is influenced by gender, family size, birth season, maternal smoking, birth weight, gestational age, and maternal diet. METHODS: Two hundred and twenty-one high risk and 308 low-risk infants were prenatally selected in a 5-year-period. Three to 5 days after birth, the total IgE was measured in capillary heel blood. RESULTS: Data on total IgE and first-degree familial predisposition were available for 170 high-risk and 300 low-risk infants. There was a statistically significant relationship between being at high-risk (maternal asthma) and increased levels of total IgE in newborns (total IgE cut-off levels: 0.6-0.9 IU/mL (odds ratio (OR)=2.1, 95% confidence interval (CI): 1.2-3.7 to 3.0, 95% CI: 1.5-5.9)), between being born in autumn and increased levels of total IgE in newborns [total IgE cut-off levels: 0.5-0.6 IU/mL (OR=2.5, 95% CI: 1.2-5.1 to 2.5, 95% CI: 1.2-5.4)] and between maternal vitamin supplements intake and decreased levels of total IgE in newborns (total IgE cut-off level: 0.9 IU/mL (OR=0.5, 95% CI:0.3-1.0)). There was no interaction between the effects of maternal asthma and birth season on total IgE, as well as between the effects of maternal asthma and maternal vitamin supplements intake. Gender, family size, maternal smoking, birth weight, and gestational age did not influence the associations. CONCLUSION; Being at high-risk of asthma (maternal asthma) and birth season are positively associated with the presence of increased levels of total IgE at birth, whereas maternal vitamin supplements intake is negatively associated with the presence of total IgE at birth.

[Relationship between the composition of fine dust particles in the air and lung function in school children]. / Relatie tussen de samenstelling van fijn stofin de lucht en de longfunctie van schoolkinderen.

OBJECTIVE: To determine whether or not there is a relationship between the lung function of school children and the ability of fine dust particles in the air to generate radicals. DESIGN: Descriptive. METHOD: Six primary schools in locations with different traffic volumes were selected in Maastricht, the Netherlands. Air samples were taken in these schools over a period of 4 days; the concentration of fine dust was measured in the 6 pooled samples. Lung function tests were performed in children in the age of 8-13 and their parents filled out a questionnaire on the state of their children's health. RESULTS: An average of 66% of the children (184 girls and 158 boys, with an average age of 10 years (range: 8-13 years)) participated. The average FEV1 for the children from the 6 schools was not related with the total amount of fine dust particles in the air. However, a lower average FEV1 was associated with a higher radical-generating capacity in the air samples. No direct association was observed between the radical-generating capacity of the dust and the traffic intensity. CONCLUSION: There was a clear relationship between lung function and the radical-generating capacity of fine dust in the air. On the basis of these findings future guidelines could be based on chemical properties of the fine dust particles and not exclusively on the quantity of fine dust.

[The treatment of asthma: indications for a change in approach]. / Behandeling van astma: aanwijzingen voor een verandering in aanpak.

In both children and adults with persistent asthma, treatment with an inhaled corticosteroid (ICS) is recommended. Moreover, inhaled bronchodilating agents have a clear role to play. The minimum effective dose of an ICS in the individual patient can be determined either by starting with a low dosage of ICS and increasing the dosage gradually on the basis of the symptoms (the 'step-up' approach), or by starting with a high dosage and, if the results are good, decreasing it to the pointwhere adequate control is maintained (the 'step-down' approach). In a study of the step-up approach with the ICS fluticasone, with or without salmeterol as a long-acting beta2-agonist (LABA) in adult patients with asthma, the approach with salmeterol produced the best results, namely, good asthma control in 71% of the patients and total control in 41%. In a study involving both children and adults with asthma, good results were obtained from treatment with a relatively low maintenance dose of ICS (budesonide) combined with a LABA (formoterol), whereby patients were permitted to use additional inhalations of the combination ICS and LABA. How the different therapeutic concepts result in long-term control, what the side effects are in the long term, and whether, in addition to the clinical symptoms, laboratory findings are also important as a therapeutic criterion are all unknown.

Chronic bronchiolitis in a 5-yr-old child after exposure to sulphur mustard gas.

Exposure to sulphur mustard (SM) gas may have extensive immediate effects on the respiratory system. However, long-term effects are far less known. This case report describes a Kurdish male child who was exposed to SM gas during a chemical attack in Iraq at 5 yrs of age. In the acute phase, the child developed severe respiratory symptoms with a chemical pneumonia. Extensive burning of the skin occurred. In the course of 10 yrs, lung function deteriorated progressively to a forced expiratory volume in one second of 30% of predicted value. Severe air-trapping occurred. The lung function abnormalities were not reversed by treatment with corticosteroids or bronchodilators. Infectious exacerbations of the child's lung disease occurred. High resolution computed tomography scan showed multiple bronchiectasis. The histological picture of an open lung biopsy was best described as a "chronic bronchiolitis".

Use of out of hours services: a comparison between two organisations.

OBJECTIVES: To investigate differences in numbers and characteristics of patients using primary or emergency care because of differences in organisation of out of hours care. BACKGROUND: Increasing numbers of self referrals at the accident and emergency (A&E) department cause overcrowding, while a substantial number of these patients exhibit minor injuries that can be treated by a general practitioner (GP). METHODS: Two different organisations of out of hours care in two Dutch cities (Heerlen and Maastricht) were investigated. Important differences between the two organisations are the accessibility and the location of primary care facility (GP cooperative). The Heerlen GP cooperative is situated in the centre of the city and is respectively 5 km and 9 km away from the two A&E departments situated in the area of Heerlen. This GP cooperative can only be visited by appointment. The Maastricht GP cooperative has free access and is located within the local A&E department. During a three week period all registration forms of patient contacts with out of hours care (GP cooperative and A&E department) were collected and with respect to the primary care patients a random sample of one third was analysed. RESULTS: For the Heerlen and Maastricht GP cooperative the annual contact rate, as extrapolated from our data, per 1000 inhabitants per year is 238 and 279 respectively (chi(2)((1df))=4.385, p=0.036). The contact rate at the A&E departments of Heerlen (n=66) and Maastricht (n=52) is not different (chi(2)((1df))=1.765, p=0.184). Some 51.7% of the patients attending the A&E department in Heerlen during out of hours were self referred, compared with 15.9% in Maastricht (chi(2)((1df))=203.13, p<0.001). CONCLUSIONS: The organisation of out of hours care in Maastricht has optimised the GP's gatekeeper function and thereby led to fewer self referrals at the A&E department, compared with Heerlen.

A molecular dosimetry approach to assess human exposure to environmental tobacco smoke in pubs.

Although the involvement of environmental tobacco smoke (ETS) in human lung cancer is no longer a matter of dispute, the magnitude of its impact still is. This is mainly due to the inefficiency of methodology to assess exposure to ETS especially in public places. Setting a real life exposure condition (3 h stay in local pubs) and using a matched-control study design, we quantified smoke-related DNA adducts in induced sputum and peripheral blood lymphocytes (PBL) of healthy non-smokers (n = 15) before and after a single pub visit by means of the (32)P-post-labeling assay. For verification, we also measured a spectrum of polycyclic aromatic hydrocarbons (PAH) in the ambient air of the pubs by personal air monitors, and determined the plasma concentrations of nicotine and cotinine by gas chromatography/mass spectrometry. The ambient air concentrations of all PAH were several orders of magnitude higher than those already reported for other indoor environments. The plasma concentrations of both nicotine and cotinine increased significantly after the pub visit (P = 0.001 and P = 0.0007, respectively). Accordingly, the overall DNA adduct profile in induced sputum, but not in PBL, changed quantitatively and qualitatively after the pub visit. Of most significance was the formation of a distinct DNA adduct in induced sputum of three individuals consequent to ETS exposure. This adduct co-migrated with the standard (+/-)-anti-benzo[a]pyrene diol epoxide-DNA adduct, which is known to form at lung cancer mutational hotspots. We conclude that real life exposure to ETS can give rise to pro-mutagenic lesions in the lower airway, and this can be best investigated in a relevant surrogate matrix such as induced sputum.

Detecting patients at a high risk of developing chronic obstructive pulmonary disease in general practice: cross sectional case finding study.

OBJECTIVES: To investigate the effectiveness of case finding of patients at risk of developing chronic obstructive pulmonary disease, whether the method is suitable for use in general practice, how patients should be selected, and the time required. DESIGN: Cross sectional study. SETTING: Two semirural general practices in the Netherlands. PARTICIPANTS: 651 smokers aged 35 to 70 years. MAIN OUTCOME MEASURES: Short standardised questionnaire on bronchial symptoms for current smokers, lung function with a spirometer, and the quality of the spirometric curve. RESULTS: Of the 201 smokers not taking drugs for a pulmonary condition, 169 produced an acceptable curve (fulfilling American Thoracic Society criteria). Of these, 30 (18%, 95% confidence interval 12% to 24%) had a forced expiratory volume in one second (FEV(1)) <80% of predicted. When smokers were preselected on the basis of chronic cough, the proportion with an FEV(1) <80% of predicted increased to 27% (17 of 64; 12% to 38%). Chronic cough was a better predictor of airflow obstruction than other symptoms, such as wheeze and dyspnoea. The presence of two symptoms was a slightly better predictor than cough only (odds ratio 3.02 (1.37 to 6.64) v 2.50 (1.14 to 5.52)). Age was also a good predictor of obstruction; smokers over 60 with cough had a 48% chance of having an obstruction. The mean time needed for spirometry was four minutes. Detecting one smoker with an FEV(1) <80% of predicted cost 5 pound sterling to 10 pound sterling. CONCLUSIONS: Trained practice assistants could check all patients who smoke for chronic obstructive pulmonary disease at little cost to the practice. Cough and age are the most important predictors of the disease. By testing one smoker a day, an average practice could identify one patient at risk a week.

Dose dependent increased mortality risk in COPD patients treated with oral glucocorticoids.

Systemic corticosteroids are often administered in COPD patients. The relationship between systemic glucocorticoids and mortality in patients with moderate to severe chronic obstructive pulmonary disease (COPD) was retrospectively analysed. Baseline characteristics of the patients, in stable clinical condition, were collected on admission to a pulmonary rehabilitation centre. Overall mortality was asessed at the end of follow-up. The Cox proportional hazards model was used to quantify the relationship between glucocorticoid use, distinguishing administration route (oral/inhalation) and oral dose, and overall mortality, adjusted for the influence of age, sex, smoking, lung function, resting arterial blood gases and body mass index. On multivariate analysis, oral glucocorticoid use at a (prednisone equivalent) dose of 10 mg x day(-1) without inhaled glucocorticoids, was associated with an increased risk (RR=2.34, 95% confidence interval (CI) 1.24-4.44) while 15 mg x day(-1) carried a relative risk of 4.03, CI = 1.99-8.15). A significant interaction was observed between inhaled and oral glucocorticoid use. Combined with inhaled glucocorticoids, the relative risk of oral glucocorticoid use appeared to be significantly smaller. It is concluded that in severe chronic obstructive pulmonary disease, maintenance treatment with oral glucocorticoids is associated with increased mortality in a dose-dependent manner. Since the present study design cannot exclude the possibility of bias by indication, further prospective studies are indicated using a broader patient characterization.

Acute effects of nebulized salbutamol on resting energy expenditure in patients with chronic obstructive pulmonary disease and in healthy subjects.

This study investigated the contribution of a single dose of salbutamol by nebulizer to the increased resting energy expenditure (REE) frequently found in patients with chronic obstructive pulmonary disease (COPD) (n = 22), in comparison with a younger (n = 15) and an older healthy (n = 10) control group. The rise in REE after nebulization of 5 mg salbutamol was significantly higher in younger (11.4%) compared to older healthy subjects (5.7%; p < 0.05) and patients with COPD (4.2%; p < 0.001), which also accounted for the increase in heart rate and the drop in the respiratory quotient. No differences in metabolic effects were found between older control subjects and patients with COPD. In conclusion, despite significant improvements in FEV1 and airway resistance, a significant rise in REE was observed in patients with COPD after nebulization of salbutamol. The metabolic effects of salbutamol were however not sufficient to explain totally the elevated REE seen in these patients.

Glucocorticoid receptor mRNA levels in bronchial epithelial cells of patients with COPD: influence of glucocorticoids.

Glucocorticoids (gcs) are known to be effective in the treatment of asthma. In chronic obstructive pulmonary disease (COPD), however, no beneficial effects are demonstrated in most patients. Hypothetically, this may be explained by an overexpressed beta-glucocorticoid receptor (GR) compared to the alpha-GR. The aim of this study was to investigate alpha- and beta-GR mRNA levels and ratios in patients with COPD with or without glucocorticoid treatment. GR and, as a control, metallothionein (MT) 2 mRNA levels were compared between patients with COPD receiving glucocorticoids (COPD + gcs), glucocorticoid naive COPD-patients (COPD - gcs) and non-COPD control patients not using gcs. Bronchoscopy was performed and bronchial epithelial cells were sampled with brushing. Smoking did not influence alpha- and beta-GR levels and ratios, nor the MT2 mRNA expression level. The alpha-GR mRNA expression was lower in the COPD - gcs group than in controls. Both GR forms were higher in the COPD + gcs patients than in the COPD - gcs patients, but not different from the levels measured in the controls. alpha 1/beta-GR mRNA ratios did not differ between the groups and averaged 1.7, suggesting no inhibitory effect of the beta-GR on the alpha 1 form. MT2 levels were upregulated in the COPD + gcs patients as compared to the COPD - gcs group, indicating a pharmacological glucocorticoid effect. In the present study it is demonstrated that basal GR mRNA levels are lower in patients with COPD. Although this needs to be investigated further, this might explain, in part, the non-responsiveness of patients with COPD to gcs.