The Mozart study: a relation between dynamic hyperinflation and physical activity in patients with chronic obstructive pulmonary disease?

BACKGROUND: Many patients with chronic obstructive pulmonary disease (COPD) experience dyspnoea during exercise, resulting in a reduction of physical activity (PA). Dynamic hyperinflation (DH) is seen as a major cause of dyspnoea in COPD. OBJECTIVE: The objective of the current study was to investigate the relationship between DH, in terms of the amount of DH and the development and recovery rate of DH in patients with COPD, and PA. METHODS: Thirty-five patients with stable COPD were included from an outpatient clinic (14 GOLD II and 21 GOLD III, median age 65). PA was assessed using an accelerometer. Subjects underwent metronome-paced tachypnoea (MPT) to induce DH. To quantify the amount of DH during MPT, a decrease in inspiratory capacity (IC) or a change in IC as percentage of total lung capacity was used. RESULTS: No significant correlations were found between the parameters describing DH and PA. Secondary correlation analyses showed a negative correlation between static hyperinflation (SH) and PA (r = -0·39; P = 0·02). The pattern of breathing during MPT and the test itself showed high interpatient variability. CONCLUSIONS: The absence of a significant correlation between DH and PA is contrary to previous studies. SH did show a correlation with PA. The variety in results and the technical difficulties in execution of the measurements ask for a new, more reliable, method to detect DH and investigate its relation with PA in patients with COPD.

Safety and Tolerability of Nebulized Amoxicillin-Clavulanic Acid in Patients with COPD (STONAC 1 and STONAC 2).

The safety and tolerability of nebulized amoxicillin clavulanic acid were determined in patients with stable COPD and during severe exacerbations of COPD. Nine stable COPD patients received doses ranging from 50:10 mg up to 300:60 mg amoxicillin clavulanic acid and eight patients hospitalised for a COPD exacerbation received fixed doses 200/40 mg twice daily. Safety was evaluated by spirometry before and after inhalation. Tolerability was evaluated by questionnaire. Plasma and expectorated sputum samples were assayed for amoxicillin content. Seventeen patients underwent in total 100 nebulizations with amoxicillin clavulanic acid. In this safety and tolerability study no clinically relevant deteriorations in FEV1 were observed. Nebulized amoxicillin clavulanic acid produces sputum concentrations well above the Minimal Inhibiting Concentration of 90% for potential pathogenic micro-organisms, with low concentrations in the central compartment (low systemic exposure). Based on spirometry and reported side effects, inhalation of nebulized amoxicillin clavulanic acid seems to be safe and well tolerated, both in stable patients with COPD as in those experiencing a severe exacerbation. Levels of amoxicillin were adequate.

Impact on clinical decision making of quality control standards applied to sputum analysis in COPD.

PURPOSE: Sputum analysis is important in COPD exacerbation management. We determined whether application of stringent quality control criteria for sputum samples had an impact on culture results. METHODS: We analyzed sputum samples of 108 patients during stable COPD and during exacerbations. To all samples quality control standards and culture interpretation rules according to the American Society of Microbiologists (ASM) were applied. RESULTS: In sputum exacerbation samples considered appropriate according to ASM quality standards, criteria for infection (40%) were met more often compared to inappropriate samples (13%) (p < 0.001). The same pattern was observed when applying these rules to sputum samples obtained during stable disease, (50% vs. 18%, p < 0.001). There was no difference in the percentage of infectious cultures obtained during the stable state and exacerbations. CONCLUSIONS: Applying stringent quality control criteria to sputum samples can have a profound effect on the labeling of sputum samples as infectious, and therefore on clinical decision making.

Legionella pneumophila pneumonia in a pregnant woman treated with anti-TNF-α antibodies for Crohn's disease: a case report.

Anti-TNF-α antibodies are widely used. The indications for their usage are still increasing. With their emerging use, their infectious complications are seen more often. We describe the first case of a pneumonia with Legionella pneumophila in a pregnant women with Crohn's disease, during treatment with anti-TNF-α antibodies. She was treated with erythromycin and made a full recovery.

Relation of sputum colour to bacterial load in acute exacerbations of COPD.

BACKGROUND: When COPD patients present with an exacerbation, one cannot verify a bacterial cause of an exacerbation without time-consuming laboratory analyses. This makes it difficult to decide up front if antibiotic treatment is needed. Therefore, in clinical practice sputum colour and purulence are often used. OBJECTIVE: To determine whether sputum colour and purulence, assessed by the Stockley colour chart, correlated with overall bacterial load in COPD patients admitted for an exacerbation. To check the robustness of the colour and purulence assessment, we correlated the changes in these parameters and the corresponding change in bacterial load in sputum over the first seven days of hospitalisation. METHODS: Twenty-two COPD patients admitted to the hospital for an exacerbation were included. During the first seven days daily sputum samples were collected. RESULTS: A very weak association between bacterial load and sputum colour was found. There was no difference in bacterial load between patients with purulent sputum or not. Also, no consistent relationship between change in sputum colour and change in bacterial load during admission was found. CONCLUSIONS: The very weak association between bacterial load and sputum colour confirms concerns over the usefulness of the colour chart. The distinction between purulent and mucoid sputum at exacerbation is insufficient for distinction between patients who are likely to benefit from antibiotic therapy and those who are not. Complementary studies are needed to determine which other, easily measurable factors can be used as predictors for an indication for use of antibiotics; sputum colour is not the one.

Self-management education for patients with chronic obstructive pulmonary disease.

BACKGROUND: There is great interest in chronic obstructive pulmonary disease (COPD) and the associated large burden of disease. COPD is characterised by frequent day by day fluctuations, and repetitive clinical exacerbations are typical. Self-management is a term applied to educational programmes aimed at teaching skills needed to carry out medical regimens specific to the disease, guide health behaviour change, and provide emotional support for patients to control their disease and live functional lives. In COPD, the value of self-management education is not yet clear. The first Cochrane review about self-management was published in 2003. It was intended to shed light on the effectiveness of self-management programmes in COPD and the relative efficacy of their constitutive elements. No conclusions about the effectiveness of self-management could be drawn because of the large variation in outcome measures used in the limited number of included studies. This article describes the first update of this review. OBJECTIVES: The objective of this review was to assess the settings, methods and efficacy of COPD self-management education programmes on health outcomes and use of health care services. SEARCH STRATEGY: We searched the Cochrane Airways Group trial register, MEDLINE (January 1985 to January 2006), reference lists, and abstracts of medical conferences. SELECTION CRITERIA: Controlled trials (randomised and non-randomised) of self-management education in patients with COPD. Studies focusing mainly on pulmonary rehabilitation and studies without usual care as a control group were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. Investigators were contacted for additional information. MAIN RESULTS: The reviewers included 15 group comparisons drawn from 14 trials. They assessed a broad-spectrum of interventions and health outcomes with different follow-up times. Meta-analyses could often not appropriately be performed because of heterogeneity among studies. The studies showed a significant reduction in the probability of at least one hospital admission among patients receiving self-management education compared to those receiving usual care (OR 0.64; 95% CI (0.47 to 0.89)). This translates into a one year NNT ranging from 10 (6 to 35) for patients with a 51% risk of exacerbation, to an NNT of 24 (16 to 80) for patients with a 13% risk of exacerbation. On the disease specific SGRQ, differences reached statistical significance at the 5% level on the total score (WMD -2.58; 95% CI (-5.14 to -0.02)) and impact domain (WMD -2.83; 95% CI (-5.65 to -0.02)), but these difference did not reach the clinically relevant improvement of 4 points. A small but significant reduction was detected in dyspnoea measured with the BORG-scale (WMD -0.53; 95% CI (-0.96 to -0.10)). No significant effects were found either in number of exacerbations, emergency department visits, lung function, exercise capacity, and days lost from work. Inconclusive results were observed in doctor and nurse visits, on symptoms other than dyspnoea, the use of courses of oral corticosteroids and antibiotics, and the use of rescue medication. AUTHORS' CONCLUSIONS: It is likely that self-management education is associated with a reduction in hospital admissions with no indications for detrimental effects in other outcome parameters. This would in itself already be enough reason for recommending self-management education in COPD. However, because of heterogeneity in interventions, study populations, follow-up time, and outcome measures, data are still insufficient to formulate clear recommendations regarding the form and contents of self-management education programmes in COPD. There is an evident need for more large RCTs with a long-term follow-up, before more conclusions can be drawn.

The role of atypical respiratory pathogens in exacerbations of chronic obstructive pulmonary disease.

The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) is heterogeneous and still under discussion. Serological studies have suggested that Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila may play a role in acute exacerbations of COPD. The presence of these atypical pathogens in sputum samples was investigated in patients with stable COPD and with acute exacerbations of COPD using real-time PCR. The present study was part of a randomised, double-blind, single-centre study and a total of 248 sputum samples from 104 COPD patients were included. In total, 122 samples obtained during stable disease (stable-state sputa) and 126 samples obtained during acute exacerbations of COPD (exacerbation sputa) were tested. Of the 122 stable-state sputa, all samples were negative for M. pneumoniae and C. pneumoniae DNA, whereas one sample was positive for Legionella non-pneumophila DNA. Of the 126 exacerbation sputa, all samples were negative for M. pneumoniae and C. pneumoniae DNA, whereas one sample was positive for Legionella non-pneumophila DNA. The possible relationship between the presence of atypical pathogens and the aetiology of acute exacerbations in chronic obstructive pulmonary disease was investigated in patients with stable disease and in those with acute exacerbations using real-time PCR. No indication was found of a role for Legionella spp., Chlamydia pneumoniae or Mycoplasma pneumoniae in stable, moderately severe chronic obstructive pulmonary disease and in its exacerbations.

Self-management education for chronic obstructive pulmonary disease.

BACKGROUND: In asthma, self-management programmes have been proven to be effective. In COPD, their value is not clear. OBJECTIVES: To assess the efficacy of COPD self-management/ education programmes on health outcomes and use of health services SEARCH STRATEGY: We searched the Cochrane Airways Group trial registers, MEDLINE (January 1985 to October 2001), reference lists, and abstracts of medical conferences. We also contacted research groups in the field for ongoing trials and unpublished material. SELECTION CRITERIA: Controlled trials (randomised and non-randomised) of self-management education in patients with COPD. Studies focusing mainly on physical pulmonary rehabilitation were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Investigators were contacted for additional information. MAIN RESULTS: The reviewers included 12 articles describing 8 randomised-controlled trials and 1 controlled clinical trial. Self-management education was compared with usual care in 8 studies. The studies in this review assessed a broad-spectrum of outcome measures with different follow-up times. Synthesis of the results using meta-analysis was always not possible. The studies showed no effect of self-management education on hospital admissions, emergency room visits, days lost from work and lung function. Inconclusive results were observed on health-related quality of life (HRQoL): studies using the disease specific SGRQ showed a better quality of life in the patients in the intervention group, but only in the activity component where there was heterogeneity between the results of the two included studies. A potential reason for the absence of convincing effects on HRQoL is the limited use of COPD-specific instruments. Inconclusive results were observed on COPD-symptoms and use of other health care resources such as doctor and nurse visits. Self-management education reduced the need for rescue medication, and led to an increased use of courses of oral steroids and antibiotics for respiratory symptoms. REVIEWER'S CONCLUSIONS: The data available for this review are insufficient for forming recommendations. Further research on the effectiveness of self-management programmes should be focussed on behavioural change evaluated in well designed randomised controlled trials with standardised outcomes designed for use in COPD patients, and with long follow-up time so that definite conclusions can be made.

Clinical and radiological evolution in patients with pulmonary Langerhans' cell histiocytosis.

BACKGROUND: Pulmonary Langerhans' cell histiocytosis (LCH) is a diffuse, smoking-related lung disease characterised pathologically by proliferation of abnormal Langerhans' cells, cyst formation and vascular abnormalities, and physiologically by a decreased diffusing capacity. The aim of this study was to describe our experience with pulmonary LCH at our institution during the past 30 years, with particular reference to diagnosis and long-term outcome. PATIENTS AND METHODS: Seven patients, two men and five women, mean age 33 years (range 26-49 years), who had been evaluated for pulmonary LCH, were retrospectively studied. All available clinical, diagnostic and pathological data were included. RESULTS: The patients presented with symptoms of dyspnoea, cough, pleuritic pain, anorexia and fatigue. Chest X-ray and high-resolution computed tomography (HRCT) showed bilateral nodular and cystic lesions, with a predilection for the middle and upper lung zones. In the majority of patients, lung function tests showed a decrease in diffusing capacity. In six patients the diagnosis of pulmonary LCH was made after immunohistochemical examination of an open lung biopsy specimen. In one patient a confident diagnosis was made radiologically. During serial follow-up, median seven years (range 1-28 years), three patients stopped smoking and in four patients the tobacco consumption remained unchanged. For the whole group the evolution was benign, with all patients being asymptomatic or showing improvement in symptoms and regression of radiological signs. CONCLUSION: Radiographic studies often provide clues to the diagnosis, but may not obviate the need for open lung biopsy in the majority of cases. Our study shows that irrespective of smoking cessation, spontaneous regression of symptoms and radiological signs and long-term survival are possible.

[Fatal miliary tuberculosis during treatment with infliximab]. / Fatale miliaire tuberculose tijdens behandeling met infliximab.

A 73-year-old woman was admitted to hospital with fever whilst under treatment with infliximab for rheumatoid arthritis. Despite repeated and specific testing, tuberculosis was only diagnosed post mortem. During infliximab therapy, latent tuberculosis can reactivate in subacute form with a possible fatal outcome. For infliximab therapy to be administered safely, the risk that the patient concerned is latently infected with tuberculosis has to be estimated beforehand; if necessary a prophylactic anti-tuberculosis treatment may be given.