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Biomedical subjects

J W J Lammers

Publications and source records attributed to J W J Lammers.

8 recordsLinked to original sources

[COPD: new insights].

Both morbidity and mortality due to chronic obstructive pulmonary disease (COPD) are increasing. In the Netherlands there are between 500,000 and 1 million patients. It has now been recognized that airway obstruction can be partially reversed and that inflammation and oxidative stress play a part in the pathophysiology. New disease outcome measures in scientific research and in the clinical setting include symptoms, quality of life, exacerbation frequency and changes in exercise tolerance. Bronchus-dilating medication is now the standard pharmacotherapy and at every stage of COPD bronchodilators administered by inhaler are advised. The introduction of long-acting beta2-agonists is an advancement in treatment. The long-term effects of tiotropium are awaited. Acetylcysteine seems to be indicated in frequent exacerbations or hyperinflation. Where non-medicinal treatment is concerned, nutrition, exercise and particularly stopping smoking are important. Company medical officers can give advice concerning work and the work situation. Home care, hospital admissions and medication are the main costs, particularly in more serious COPD.

Bronchodilator Agents↗

[The increase in pneumonia-related morbidity and mortality among adults in the Netherlands and possible explanations for it].

As seen in several national registration systems, the morbidity and mortality due to pneumonia-related disease has increased in the Netherlands in the past 10 years. It is unlikely that the observed increase in mortality due to pneumonia is purely the result of the registration system used or misclassification. An increase in the elderly population is the most likely, albeit only partial, explanation. An increase in underlying diseases such as chronic obstructive pulmonary disease and diabetes mellitus is also a possible explanation. Increased antibiotic resistance, inadequate treatment or a shift in the spectrum of micro-organisms causing pneumonia are less likely explanations. Reducing the morbidity and mortality due to pneumonia demands an integrated approach aimed at elderly patients or patients with co-existing disease and executed by specialists in the fields of geriatrics, internal medicine, pulmonary disease and infectious diseases.

Aged↗

Persistence with inhaled corticosteroid therapy in daily practice.

OBJECTIVE: To quantify persistence with inhaled corticosteroids (ICS) among new users in daily practice and identify determinants of persistence. METHODS: A retrospective cohort study was performed with data from the Dutch PHARMO system. This system consists of medication and hospital admission records of 325,000 inhabitants of 12 Dutch cities. In patients who were already using other drugs with a labeled indication of obstructive lung diseases (ATC: R03), individuals with a first dispensing of ICS between January 1, 1994 and December 31, 2000 were identified. Persistence with ICS was defined as the number of days on ICS treatment in the first year of use. Determinants of persistence were identified one year before start of the first dispensing of ICS. RESULTS: Approximately 50% of the patients used inhaled corticosteroids (ICS) for less than 200 days, while 18% continued treatment for one year. One-year persistence rates increased to 40% in patients with a history of multiple respiratory disease related drugs. Persistence rates also increased with lower initial doses, if the initial prescription was instituted by a medical specialist, if a patient was previously hospitalized for obstructive lung diseases, and with increasing age. CONCLUSION: The persistence rate of ICS is poor. Preventing early treatment discontinuation may be important to ensure maximal benefit from ICS treatment.

Administration, Inhalation↗

Duration of effect of single-dose inhaled fluticasone propionate on AMP-induced bronchoconstriction.

Airway hyperresponsiveness induced by adenosine-5'-monophosphate (AMP) is regarded as a reliable model for allergic asthma and for the evaluation of anti-asthmatic drugs. Single-dose inhaled corticosteroids (ICS) are known to be protective in this model, but the duration of action of these drugs in this model has never been studied. The duration of ICS protection was determined by administration of single-dose fluticasone propionate (FP; 1,000 micrograms) up to 26 h before AMP challenge. A randomised, double-blind, placebo-controlled, four-way crossover study was performed in 13 mild asthmatics (mean +/- SD predicted forced expiratory volume in one second (FEV1) 98 +/- 7%). Each subject received placebo and FP (at 26, 14 or 2 h prior to the AMP challenge). Furthermore, the marker exhaled nitric oxide (eNO) was studied after administration at these time points to investigate whether eNO also demonstrates the duration of action of ICS. The doubling concentrations difference (DCD) of AMP causing a 20% fall in FEV1, when FP was administered 26, 14 or 2 h prior to challenge, was significantly increased as compared with placebo: DCD (95% confidence interval) at 26 h, 0.73 (0.20-1.26), p = 0.008; 14 h, 1.50 (0.99-2.01), p < 0.001; and 2 h, 2.89 (2.37-3.40), p < 0.001. However, eNO was not significantly affected at these time points. In conclusion, a single dose of 1,000 micrograms inhaled fluticasone propionate protects against adenosine-5'-monophosphate airway hyperresponsiveness up to 26 h after dosing. This study suggests that adenosine-5'-monophosphate challenge can be used as a sensitive marker to study the duration of action of inhaled corticosteroids.

Adenosine Monophosphate↗

Conventional influenza vaccination is not associated with complications in working-age patients with asthma or chronic obstructive pulmonary disease.

By using a nested case-control design, the authors studied the effectiveness of the influenza vaccine in reducing severe and fatal complications in 4,241 and 5,966 primary care, working-age patients aged 18-64 years who had asthma or chronic obstructive pulmonary disease during the 1998-1999 and 1999-2000 influenza epidemics in the Netherlands. Patients developing fatal or nonfatal exacerbations of lung disease, pneumonia, congestive heart failure, or myocardial infarction during either epidemic were considered cases. For each case, four age- and sex-matched controls were randomly sampled, and patient records were reviewed. Conditional logistic regression and propensity scores were used to assess vaccine effectiveness after adjustment for confounding factors. In seasons one and two, respectively, 87% (47/54) and 85% (171/202) of the cases and 74% (155/210) and 75% (575/766) of the controls had been vaccinated. After adjustments, vaccination was not associated with reductions in complications (season one: odds ratio = 0.95, 95% confidence interval (CI): 0.26, 3.48; season two: odds ratio = 1.07, 95% CI: 0.59, 1.96; pooled odds ratio = 1.07, 95% CI: 0.63, 1.80). Because influenza vaccination appeared not to be associated with a clinically relevant reduction in severe morbidity, other measures need to be explored.

Adolescent↗

Lung function changes and pulmonary complications in patients with stage III non-small cell lung cancer treated with gemcitabine/cisplatin as part of combined modality treatment.

INTRODUCTION: Lung cancer is the leading cause of cancer mortality. Chemotherapy, ideally a platinum-based regimen as part of combined modality treatment, is appropriate for selected patients with locally advanced stage III non-small cell lung cancer (NSCLC) who have a good performance status. However, chemotherapy can induce side effects including lung function changes. AIM OF THE STUDY: Retrospective analysis of lung function changes in 44 patients with stage III NSCLC treated with neoadjuvant chemotherapy (NCT) followed by surgery and/or radiotherapy. PATIENTS AND METHODS: NCT consisted of three cycles of gemcitabine/cisplatin. The following data were analysed: age, sex, the presence of chronic obstructive pulmonary disease (COPD), smoking behaviour, response, complications after surgery and/or radiotherapy, and VC, FEV(1), DL(co) and K(co) before and after chemotherapy. DL(co) values were corrected for haemoglobin concentrations. RESULTS: We found a significant decline of K(co) (-13.5% of pred; 95% CI: -16.6 to -10.4; P<0.0001), independent of tumor response or presence and severity of COPD. FEV(1) and FEV(1)/VC showed significant increases irrespective of tumor response. Significantly more pulmonary complications were recorded in the radiotherapy group after NCT (P=0.009) compared to patients who underwent surgical therapy after NCT. CONCLUSIONS: Patients diagnosed with NSCLC stadium III who were treated with NCT consisting of cisplatin and gemcitabine showed a significant decline of DL(co) and K(co), irrespective of tumor response, presence and severity of COPD, sex and number of cycles of chemotherapy. Significantly more pulmonary complications were seen in patients treated with NCT and radiotherapy compared with patients treated with NCT and surgery. Questions concering the pathophysiological mechanisms of lung function changes and long term follow-up of pulmonary toxicity due to NCT remain still unanswered and have to be subject of future studies.

Adult↗

Systemic inflammation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammation in the pulmonary tissue. The disease is associated with a switch from a self-limiting inflammatory response, mainly initiated by smoke inhalation, to a chronic persistent inflammatory response after prolonged interaction with cigarette smoke. The extent of the inflammatory reaction is correlated with the severity of the disease. Chronic inflammation in the pulmonary tissue is also associated with systemic effects. These effects range from cytokine-induced priming of peripheral leukocytes, to muscle wasting induced by cytokines such as tumour necrosis factor-alpha. Despite a general consensus that chronic inflammation is a characteristic phenomenon of the disease, surprisingly little is known regarding the underlying pathogenetic mechanisms. A clear communication is present between the disease mechanisms in the pulmonary compartment and peripheral tissues, leading to the concept of COPD as a systemic inflammatory disease. This communication can be mediated by: 1) leakage of reactive oxygen species and stress-induced cytokines directly into the peripheral blood, 2) (pre)activation of peripheral blood leukocytes that can result in aberrant homing and activation of inflammatory cells in distant tissues, and 3) the liberation of proinflammatory mediators by leukocytes and/or stromal cells present in the pulmonary tissues during progression of the disease. The current authors hypothesise that the occurrence of a chronic inflammatory response after prolonged interaction of the pulmonary tissue with cigarette smoke causes aberrant homing of leukocytes to the tissue and delayed apoptosis. This leads to the autonomous characteristic of the inflammatory response in patients with chronic obstructive pulmonary disease.

Humans↗

N-acetylcysteine reduces the risk of re-hospitalisation among patients with chronic obstructive pulmonary disease.

The aim of this study was to evaluate the effect of oral N-acetylcysteine in the prevention of re-hospitalisation for chronic obstructive pulmonary disease (COPD) exacerbations. Using the PHARmacoMOrbidity linkage (PHARMO) system the authors included all patients aged > or = 55 yrs who had been dispensed medication, labelled for respiratory indications (anatomical therapeutic chemical (ATC) classification system: R03), between 1986-1998 and who had also been hospitalised for COPD (International Classification of Diseases (ICD)-9: 491, 492, 496) in this time frame. These subjects were subsequently divided into two groups, those who had received N-acetylcysteine following discharge from their first admission between 1986-1998 and those who had not. All the patients were studied starting from their initial discharge, until their first readmission, death or end of data collection period. The maximum follow-up period was 1 yr. A total of 1,219 patients, who were hospitalised for COPD between 1986-1998, were included in this study. After adjustment for disease severity, it was observed that the use of N-acetylcysteine was significantly associated with a reduced risk of readmission. The readmission risk was significantly lower in patients with high average daily doses of N-acetylcysteine. In conclusion it was observed that N-acetylcysteine reduces the risk of rehospitalisation for chronic obstructive pulmonary disease by approximately 30% and that this risk reduction is dose-dependent.

Acetylcysteine↗